dbSNP rs1440893408: SLX1A:p.Ala106Asp (chr16-30194962-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001014999.3(SLX1A):c.317C>A(p.Ala106Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A106G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 21)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLX1A
NM_001014999.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.02

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15421414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLX1A	NM_001014999.3 link	c.317C>A	p.Ala106Asp	missense_variant	Exon 3 of 6	ENST00000251303.11	NP_001014999.1	Q9BQ83-1
SLX1A	NM_001015000.2 link	c.240+171C>A		intron_variant	Intron 2 of 4		NP_001015000.1	Q9BQ83-2
SLX1A-SULT1A3	NR_037608.1 link	n.436C>A		non_coding_transcript_exon_variant	Exon 2 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLX1A	ENST00000251303.11 link	c.317C>A	p.Ala106Asp	missense_variant	Exon 3 of 6	1	NM_001014999.3	ENSP00000251303.7		Q9BQ83-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150628

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000243

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1261356

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

618938

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000663

AC:

AN:

150744

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73586

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.031

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.49

FATHMM_MKL

Uncertain

0.84

M_CAP

Benign

0.024

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.3

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.7

REVEL

Benign

0.044

Sift

Benign

0.61

Sift4G

Benign

0.56

Vest4

0.20

MutPred

0.44

Loss of MoRF binding (P = 0.0471);

MVP

0.043

MPC

2.5

ClinPred

0.11

GERP RS

2.9

Varity_R

0.22

gMVP

0.63

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over