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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 frequency of 0.224 in 152,408 control chromosomes in the GnomAD database, including 4,064 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as (no 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: 95 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005432.4. You can select a different transcript below to see updated ACMG 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	NP_005423.1	O43542
	XRCC3	NM_005432.4	MANE Select	c.-316A>G		5_prime_UTR	Exon 2 of 10	NP_005423.1	O43542
	XRCC3	NM_001371231.1		c.-410A>G		splice_region	Exon 2 of 10	NP_001358160.1	Q53XC8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC3	ENST00000555055.6	TSL:1 MANE Select	c.-316A>G		splice_region	Exon 2 of 10	ENSP00000452598.1	O43542
	XRCC3	ENST00000555055.6	TSL:1 MANE Select	c.-316A>G		5_prime_UTR	Exon 2 of 10	ENSP00000452598.1	O43542
	KLC1	ENST00000348520.10	TSL:1	c.*11731T>C		3_prime_UTR	Exon 15 of 15	ENSP00000341154.6	Q07866-1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34020 AN: 152084 Hom.: 4052 Cov.: 34

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.234

GnomAD4 exome AF: 0.275 AC: 56 AN: 204 Hom.: 6 Cov.: 0 AF XY: 0.279 AC XY: 43 AN XY: 154

African (AFR) AF: 0.500 AC: 3 AN: 6

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 0.400 AC: 4 AN: 10

European-Finnish (FIN) AF: 0.417 AC: 5 AN: 12

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.253 AC: 42 AN: 166

Other (OTH) AF: 0.00 AC: 0 AN: 8

GnomAD4 genome AF: 0.224 AC: 34029 AN: 152204 Hom.: 4058 Cov.: 34 AF XY: 0.229 AC XY: 17042 AN XY: 74428

African (AFR) AF: 0.232 AC: 9630 AN: 41522

American (AMR) AF: 0.193 AC: 2946 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 868 AN: 3472

East Asian (EAS) AF: 0.468 AC: 2416 AN: 5164

South Asian (SAS) AF: 0.368 AC: 1779 AN: 4832

European-Finnish (FIN) AF: 0.237 AC: 2520 AN: 10612

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13168 AN: 67988

Other (OTH) AF: 0.238 AC: 502 AN: 2112

Alfa AF: 0.212 Hom.: 3332

Bravo AF: 0.219

Asia WGS AF: 0.416 AC: 1445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.76
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000075
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1799794; hg19: chr14-104179267;