20-1915372-C-T

Position:

chr20-1915372-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001040023.2(SIRPA):c.353C>T(p.Thr118Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000458 in 1,609,758 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00046 ( 1 hom. )

Consequence

SIRPA
NM_001040023.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.104

Variant links:

Genes affected

SIRPA (HGNC:9662): (signal regulatory protein alpha) 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. This protein can be phosphorylated by tyrosine kinases. The phospho-tyrosine residues of this PTP have been shown to recruit SH2 domain containing tyrosine phosphatases (PTP), and serve as substrates of PTPs. This protein was found to participate in signal transduction mediated by various growth factor receptors. CD47 has been demonstrated to be a ligand for this receptor protein. This gene and its product share very high similarity with several other members of the SIRP family. These related genes are located in close proximity to each other on chromosome 20p13. Multiple alternatively spliced transcript variants have been determined for this gene. [provided by RefSeq, Jul 2008]

SIRPA links:

Genome browser will be placed here

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=0.1403766).

BP6

Variant 20-1915372-C-T is Benign according to our data. Variant chr20-1915372-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3025288.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIRPA	NM_001040023.2 linkuse as main transcript	c.353C>T	p.Thr118Ile	missense_variant	2/8	ENST00000358771.5	NP_001035112.1	P78324-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SIRPA	ENST00000358771.5 linkuse as main transcript	c.353C>T	p.Thr118Ile	missense_variant	2/8	1	NM_001040023.2	ENSP00000351621.4	P78324-1
SIRPA	ENST00000356025.7 linkuse as main transcript	c.353C>T	p.Thr118Ile	missense_variant	3/9	1		ENSP00000348307.3	P78324-1
SIRPA	ENST00000400068.7 linkuse as main transcript	c.353C>T	p.Thr118Ile	missense_variant	3/9	1		ENSP00000382941.4	P78324-1
SIRPA	ENST00000622179.4 linkuse as main transcript	c.353C>T	p.Thr118Ile	missense_variant	3/9	5		ENSP00000478763.1	P78324-2

Frequencies

GnomAD3 genomes

AF:

0.000451

AC:

AN:

148702

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000148

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000136

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000439

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000819

Gnomad OTH

AF:

0.000979

GnomAD4 exome

AF:

0.000459

AC:

670

AN:

1460936

Hom.:

Cov.:

AF XY:

0.000432

AC XY:

314

AN XY:

726808

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000543

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.000450

AC:

AN:

148822

Hom.:

Cov.:

AF XY:

0.000428

AC XY:

AN XY:

72478

show subpopulations

Gnomad4 AFR

AF:

0.000147

Gnomad4 AMR

AF:

0.000136

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000440

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000819

Gnomad4 OTH

AF:

0.000969

Alfa

AF:

0.000612

Hom.:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000699

AC:

ExAC

AF:

0.000486

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

SIRPA: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

T;.;T;T

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.79

T;T;.;.

M_CAP

Benign

0.041

MetaRNN

Benign

0.14

T;T;T;T

MetaSVM

Benign

-0.48

MutationAssessor

Benign

1.8

L;L;L;L

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-4.3

D;.;D;D

REVEL

Benign

0.20

Sift

Benign

0.094

T;.;T;T

Sift4G

Benign

0.12

T;T;T;T

Polyphen

0.14

B;D;B;B

Vest4

0.13

MVP

0.75

MPC

0.70

ClinPred

0.10

GERP RS

0.88

Varity_R

0.21

gMVP

0.61

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