Genetic Variant SLA2:p.Thr125Asn (chr20-36632603-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_032214.4(SLA2):c.374C>A(p.Thr125Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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. T125I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLA2
NM_032214.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.932

Publications

0 publications found

Variant links:

Genes affected

SLA2 (HGNC:17329): (Src like adaptor 2) This gene encodes a member of the SLAP family of adapter proteins. The encoded protein may play an important receptor-proximal role in downregulating T and B cell-mediated responses and inhibits antigen receptor-induced calcium mobilization. This protein interacts with Cas-Br-M (murine) ecotropic retroviral transforming sequence c. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

SLA2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33263806).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032214.4. 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
	SLA2	NM_032214.4	MANE Select	c.374C>A	p.Thr125Asn	missense	Exon 5 of 8	NP_115590.1	Q9H6Q3-1
	SLA2	NM_175077.3		c.374C>A	p.Thr125Asn	missense	Exon 5 of 8	NP_778252.1	Q9H6Q3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLA2	ENST00000262866.9	TSL:1 MANE Select	c.374C>A	p.Thr125Asn	missense	Exon 5 of 8	ENSP00000262866.4	Q9H6Q3-1
SLA2	ENST00000948638.1		c.374C>A	p.Thr125Asn	missense	Exon 5 of 9	ENSP00000618697.1
SLA2	ENST00000948639.1		c.374C>A	p.Thr125Asn	missense	Exon 4 of 7	ENSP00000618698.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461518

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727086

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111706

Other (OTH)

AF:

0.00

AC:

AN:

60388

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.63

Eigen

Benign

0.078

Eigen_PC

Benign

-0.030

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.82

M_CAP

Benign

0.023

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.9

PhyloP100

0.93

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.14

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.035

Polyphen

0.96

Vest4

0.29

MutPred

0.44

Loss of phosphorylation at T125 (P = 0.031)

MVP

0.64

MPC

0.70

ClinPred

0.98

GERP RS

-2.0

Varity_R

0.53

gMVP

0.62

Mutation Taster

=42/58

disease causing

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over