20-1630272-T-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_018556.4(SIRPG):c.1116A>T(p.Ile372=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 1,573,640 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0074 (7 hom., cov: 32)
  • Exomes 𝑓: 0.011 (123 hom.)
• Consequence: SIRPG NM_018556.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.317

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 20-1630272-T-A is Benign according to our data. Variant chr20-1630272-T-A is described in ClinVar as [Benign]. Clinvar id is 2652136.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.317 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIRPG	NM_018556.4	c.1116A>T	p.Ile372=	synonymous_variant	5/6	ENST00000303415.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIRPG	ENST00000303415.7	c.1116A>T	p.Ile372=	synonymous_variant	5/6	1	NM_018556.4	P2

Frequencies

GnomAD3 genomes AF: 0.00741 AC: 1126 AN: 152052 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00220

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00353

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00971

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0125

Gnomad OTH AF: 0.00670

GnomAD3 exomes AF: 0.00767 AC: 1451 AN: 189104 Hom.: 15 AF XY: 0.00749 AC XY: 752 AN XY: 100342

Gnomad AFR exome AF: 0.00162

Gnomad AMR exome AF: 0.00387

Gnomad ASJ exome AF: 0.00280

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00175

Gnomad FIN exome AF: 0.0103

Gnomad NFE exome AF: 0.0131

Gnomad OTH exome AF: 0.00660

GnomAD4 exome AF: 0.0113 AC: 16028 AN: 1421470 Hom.: 123 Cov.: 32 AF XY: 0.0110 AC XY: 7743 AN XY: 703158

Gnomad4 AFR exome AF: 0.00149

Gnomad4 AMR exome AF: 0.00428

Gnomad4 ASJ exome AF: 0.00300

Gnomad4 EAS exome AF: 0.0000264

Gnomad4 SAS exome AF: 0.00192

Gnomad4 FIN exome AF: 0.0111

Gnomad4 NFE exome AF: 0.0132

Gnomad4 OTH exome AF: 0.00945

GnomAD4 genome AF: 0.00740 AC: 1126 AN: 152170 Hom.: 7 Cov.: 32 AF XY: 0.00686 AC XY: 510 AN XY: 74394

Gnomad4 AFR AF: 0.00219

Gnomad4 AMR AF: 0.00353

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00971

Gnomad4 NFE AF: 0.0125

Gnomad4 OTH AF: 0.00664

Alfa AF: 0.0107 Hom.: 1

Bravo AF: 0.00711

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

SIRPG: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.68
Dann	Benign	0.73

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

Other links and lift over

dbSNP: rs34442420; hg19: chr20-1610918;