rs1799794

Variant names:

• chr14-103712930-T-C
• rs1799794
• NM_005432.4:c.-316A>G

Your query was ambiguous. Multiple possible variants found:

• chr14-103712930-T-C
• chr14-103712930-T-A

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_005432.4(XRCC3):c.-316A>G variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.224 (AC=34,085) in the gnomAD database across 152,408 control chromosomes, including 4,064 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.452. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain Significance (no review stars).

• Frequency:
  • Genomes: 𝑓 0.22 (4058 hom., cov: 34)
  • Exomes 𝑓: 0.27 (6 hom.)
• Consequence: XRCC3 NM_005432.4 splice_region
• Scores: Splicing: ADA: 0.00007478
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.429
• Publications: 96 publications found

Genes affected

XRCC3 (HGNC:12830): (X-ray repair cross complementing 3) This gene encodes a member of the RecA/Rad51-related protein family that participates in homologous recombination to maintain chromosome stability and repair DNA damage. This gene functionally complements Chinese hamster irs1SF, a repair-deficient mutant that exhibits hypersensitivity to a number of different DNA-damaging agents and is chromosomally unstable. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

KLC1 (HGNC:6387): (kinesin light chain 1) Conventional kinesin is a tetrameric molecule composed of two heavy chains and two light chains, and transports various cargos along microtubules toward their plus ends. The heavy chains provide the motor activity, while the light chains bind to various cargos. This gene encodes a member of the kinesin light chain family. It associates with kinesin heavy chain through an N-terminal domain, and six tetratricopeptide repeat (TPR) motifs are thought to be involved in binding of cargos such as vesicles, mitochondria, and the Golgi complex. Thus, kinesin light chains function as adapter molecules and not motors per se. Although previously named "kinesin 2", this gene is not a member of the kinesin-2 / kinesin heavy chain subfamily of kinesin motor proteins. Extensive alternative splicing produces isoforms with different C-termini that are proposed to bind to different cargos; however, the full-length nature and/or biological validity of most of these variants have not been determined. [provided by RefSeq, Jul 2008]

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Benign. The variant received -12 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.4523 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_005432.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	XRCC3 NM_005432.4	MANE Select	c.-316A>G	splice_region	Exon 2 of 10	Prot: NP_005423.1 UniProt:
	XRCC3 NM_005432.4	MANE Select	c.-316A>G	5_prime_UTR	Exon 2 of 10	Prot: NP_005423.1 UniProt:
	XRCC3 NM_001371231.1		c.-410A>G	splice_region	Exon 2 of 10	Prot: NP_001358160.1 UniProt:

XRCC3 NM_005432.4

MANE Select

HGVSc / HGVSpc.-316A>G

Exon rankExon 2 of 10

splice_region

Prot: NP_005423.1UniProt: Q53XC8O43542

XRCC3 NM_005432.4

MANE Select

HGVSc / HGVSpc.-316A>G

Exon rankExon 2 of 10

5_prime_UTR

Prot: NP_005423.1UniProt: Q53XC8O43542

XRCC3 NM_001371231.1

HGVSc / HGVSpc.-410A>G

Exon rankExon 2 of 10

splice_region

Prot: NP_001358160.1UniProt: Q53XC8O43542

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	XRCC3 ENST00000555055.6	TSL:1MANE Select	c.-316A>G	splice_region	Exon 2 of 10	Prot: ENSP00000452598.1 UniProt:
	XRCC3 ENST00000555055.6	TSL:1MANE Select	c.-316A>G	5_prime_UTR	Exon 2 of 10	Prot: ENSP00000452598.1 UniProt:
	KLC1 ENST00000348520.10	TSL:1	c.*11731T>C	3_prime_UTR	Exon 15 of 15	Prot: ENSP00000341154.6 UniProt:

XRCC3 ENST00000555055.6

TSL:1MANE Select

HGVSc / HGVSpc.-316A>G

Exon rankExon 2 of 10

splice_region

Prot: ENSP00000452598.1UniProt: O43542

XRCC3 ENST00000555055.6

TSL:1MANE Select

HGVSc / HGVSpc.-316A>G

Exon rankExon 2 of 10

5_prime_UTR

Prot: ENSP00000452598.1UniProt: O43542

KLC1 ENST00000348520.10

TSL:1

HGVSc / HGVSpc.*11731T>C

Exon rankExon 15 of 15

3_prime_UTR

Prot: ENSP00000341154.6UniProt: Q07866-1

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 5 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.224	AC:34020	Hom:4052	AN:152084	Cov:34
GnomAD4 exome	AF: 0.275	AC:56	Hom:6	AN:204	Cov:0
GnomAD4 genome	AF: 0.224	AC:34029	Hom:4058	AN:152204	Cov:34
TOPMed (Bravo)	AF: 0.219	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.212	AC:37205	Hom:4057	AN:175526	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.221	AC:517	Hom:58	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.476	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.753	AC:61	Hom:	AN:81	Cov:
GenomeAsia100K	AF: 0.416	AC:1445	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.518	AC:3746	Hom:	AN:7234	Cov:
Qatari Genome	AF: 0.301	AC:53	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.477	AC:58567	Hom:14101	AN:122724	Cov:
Turkish Variome	AF: 0.223	AC:345	Hom:35	AN:1546	Cov:
UK10K	AF: 0.187	AC:1412	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.476	AC:4266	Hom:1042	AN:8960	Cov:

Showing 15 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
SCHEMA(Schizophrenia)	0.0911	2087	22914	0.0442	1312	29652

Showing 1 cohortAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	7.9
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.76
GPN-Star LLR	N/A	-0.052
GPN-Star score	N/A	0.052
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	-0.43

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
dbscSNV1_ADA	Benign	0.000075
Pangolin (max)	Benign	0.010
SpliceAI score (max)	Benign	0.020	Details are displayed if max score is > 0.2

Showing 3 of 3 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs1799794;

hg19: chr14-104179267;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar