Variant 20-1636446-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018556.4(SIRPG):c.490G>A(p.Val164Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000638 in 1,614,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

SIRPG
NM_018556.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.865

Variant links:

Genes affected

SIRPG (HGNC:15757): (signal regulatory protein gamma) The protein encoded by this gene is a member of the signal-regulatory protein (SIRP) family, and also belongs to the immunoglobulin superfamily. SIRP family members are receptor-type transmembrane glycoproteins known to be involved in the negative regulation of receptor tyrosine kinase-coupled signaling processes. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

SIRPG links:

SIRPG-AS1 (HGNC:51229): (SIRPG antisense RNA 1)

SIRPG-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.045865804).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIRPG	NM_018556.4 link	c.490G>A	p.Val164Met	missense_variant	3/6	ENST00000303415.7	NP_061026.2	Q9P1W8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIRPG	ENST00000303415.7 link	c.490G>A	p.Val164Met	missense_variant	3/6	1	NM_018556.4	ENSP00000305529.3		Q9P1W8-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152230

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:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000147

AC:

AN:

251490

Hom.:

AF XY:

0.000184

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00114

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000684

AC:

100

AN:

1461894

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00107

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.000140

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 28, 2023

The c.490G>A (p.V164M) alteration is located in exon 3 (coding exon 3) of the SIRPG gene. This alteration results from a G to A substitution at nucleotide position 490, causing the valine (V) at amino acid position 164 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

.;T;.;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.053

LIST_S2

Uncertain

0.89

D;D;D;.

M_CAP

Benign

0.0016

MetaRNN

Benign

0.046

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.2

.;M;M;M

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-2.4

N;N;N;N

REVEL

Benign

0.085

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Uncertain

0.020

D;D;D;D

Polyphen

0.97, 0.98

.;D;D;D

Vest4

0.35

MutPred

0.59

.;Gain of disorder (P = 0.0788);Gain of disorder (P = 0.0788);Gain of disorder (P = 0.0788);

MVP

0.16

MPC

0.18

ClinPred

0.20

GERP RS

1.1

Varity_R

0.30

gMVP

0.58

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over