chr16-30197272-G-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PP3_Strong

The NM_001014999.3(SLX1A):c.713G>C(p.Cys238Ser) variant causes a missense, splice region change. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000081 ( 0 hom., cov: 18)

Exomes 𝑓: 0.000042 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLX1A
NM_001014999.3 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.81

Publications

0 publications found

Variant links:

Genes affected

SLX1A (HGNC:20922): (SLX1 homolog A, structure-specific endonuclease subunit) This gene encodes a protein that is an important regulator of genome stability. The protein represents the catalytic subunit of the SLX1-SLX4 structure-specific endonuclease, which can resolve DNA secondary structures that are formed during repair and recombination processes. Two identical copies of this gene are located on the p arm of chromosome 16 due to a segmental duplication; this record represents the more centromeric copy. Alternative splicing results in multiple transcript variants. Read-through transcription also occurs between this gene and the downstream SULT1A3 (sulfotransferase family, cytosolic, 1A, phenol-preferring, member 3) gene. [provided by RefSeq, Nov 2010]

SLX1A links:

SLX1A-SULT1A3 (HGNC:44437): (SLX1A-SULT1A3 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring SLX1A (SLX1 structure-specific endonuclease subunit homolog A) and SULT1A3 (sulfotransferase family, cytosolic, 1A, phenol-preferring, member 3) genes on the short arm of chromosome 16. A duplicate read-through locus also exists between the SLX1B and SULT1A4 genes located approximately 730 kb upstream on the same chromosome. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2017]

SLX1A-SULT1A3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.968

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001014999.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLX1A	NM_001014999.3	MANE Select	c.713G>C	p.Cys238Ser	missense splice_region	Exon 5 of 6	NP_001014999.1	Q9BQ83-1
SLX1A	NM_001015000.2		c.371G>C	p.Cys124Ser	missense splice_region	Exon 4 of 5	NP_001015000.1	Q9BQ83-2
SLX1A-SULT1A3	NR_037608.1		n.832G>C		splice_region non_coding_transcript_exon	Exon 4 of 11

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLX1A	ENST00000251303.11	TSL:1 MANE Select	c.713G>C	p.Cys238Ser	missense splice_region	Exon 5 of 6	ENSP00000251303.7	Q9BQ83-1
SLX1A	ENST00000345535.9	TSL:1	c.371G>C	p.Cys124Ser	missense splice_region	Exon 4 of 5	ENSP00000333945.4	Q9BQ83-2
SLX1A	ENST00000941762.1		c.770G>C	p.Cys257Ser	missense splice_region	Exon 5 of 6	ENSP00000611821.1

Frequencies

GnomAD3 genomes

AF:

0.00000811

AC:

AN:

123244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000173

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000891

AC:

AN:

157152

AF XY:

0.000119

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000253

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000417

AC:

AN:

863952

Hom.:

Cov.:

AF XY:

0.0000515

AC XY:

AN XY:

446730

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15200

American (AMR)

AF:

0.00

AC:

AN:

38148

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20398

East Asian (EAS)

AF:

0.00

AC:

AN:

38254

South Asian (SAS)

AF:

0.000509

AC:

AN:

70662

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48234

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3966

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

589070

Other (OTH)

AF:

0.00

AC:

AN:

40020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.422

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000811

AC:

AN:

123244

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

60300

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

27576

American (AMR)

AF:

0.00

AC:

AN:

13452

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3124

East Asian (EAS)

AF:

0.00

AC:

AN:

5094

South Asian (SAS)

AF:

0.00

AC:

AN:

4338

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9198

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.0000173

AC:

AN:

57644

Other (OTH)

AF:

0.00

AC:

AN:

1752

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000271

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Benign

-0.048

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.48

Eigen

Pathogenic

0.75

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.94

M_CAP

Pathogenic

0.32

MetaRNN

Pathogenic

0.97

MetaSVM

Benign

-0.43

MutationAssessor

Pathogenic

3.4

PhyloP100

5.8

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-7.2

REVEL

Pathogenic

0.69

Sift

Uncertain

0.012

Sift4G

Pathogenic

0.0

Vest4

0.92

MutPred

0.80

Gain of disorder (P = 0.022)

MVP

0.20

MPC

3.7

ClinPred

0.91

GERP RS

2.5

Varity_R

0.95

gMVP

0.80

Mutation Taster

=66/34

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over