rs370463374

Variant names:

• chr20-1636220-C-G
• rs370463374
• NM_018556.4:c.716G>C

Your query was ambiguous. Multiple possible variants found:

• chr20-1636220-C-G
• chr20-1636220-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018556.4(SIRPG):​c.716G>C​(p.Arg239Pro) 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. 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. R239H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SIRPG NM_018556.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.984

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42254117).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRPG	NM_018556.4	c.716G>C	p.Arg239Pro	missense_variant	Exon 3 of 6	ENST00000303415.7	NP_061026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRPG	ENST00000303415.7	c.716G>C	p.Arg239Pro	missense_variant	Exon 3 of 6	1	NM_018556.4	ENSP00000305529.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 66

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.079	.;T;.;.
Eigen	Benign	-0.033
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.32	N
LIST_S2	Uncertain	0.91	D;D;D;.
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.42	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.3	.;M;M;M
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-5.2	D;D;D;D
REVEL	Benign	0.12
Sift	Uncertain	0.015	D;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D
Polyphen		1.0, 0.99	.;D;D;D
Vest4		0.42
MutPred		0.57		.;Gain of glycosylation at R239 (P = 0.0496);Gain of glycosylation at R239 (P = 0.0496);Gain of glycosylation at R239 (P = 0.0496);
MVP		0.59
MPC		0.20
ClinPred		0.98	D
GERP RS		0.96
Varity_R		0.57
gMVP		0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs370463374; hg19: chr20-1616866;