NM_018556.4:c.695C>A

Variant names:

• chr20-1636241-G-T
• NM_018556.4:c.695C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018556.4(SIRPG):​c.695C>A​(p.Thr232Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SIRPG NM_018556.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.44
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018556.4. 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
	SIRPG	NM_018556.4	MANE Select	c.695C>A	p.Thr232Asn	missense	Exon 3 of 6	NP_061026.2	Q9P1W8-1
	SIRPG	NM_001039508.2		c.695C>A	p.Thr232Asn	missense	Exon 3 of 5	NP_001034597.1	Q9P1W8-4
	SIRPG	NM_080816.3		c.431-5935C>A		intron	N/A	NP_543006.2	Q9P1W8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRPG	ENST00000303415.7	TSL:1 MANE Select	c.695C>A	p.Thr232Asn	missense	Exon 3 of 6	ENSP00000305529.3	Q9P1W8-1
	SIRPG	ENST00000381580.5	TSL:1	c.596C>A	p.Thr199Asn	missense	Exon 3 of 6	ENSP00000370992.1	Q9P1W8-2
	SIRPG	ENST00000216927.4	TSL:1	c.695C>A	p.Thr232Asn	missense	Exon 3 of 4	ENSP00000216927.4	Q9P1W8-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 69

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.0073
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0043	T
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		4.4
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.14
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.99	D
Vest4		0.37
MutPred		0.62		Gain of disorder (P = 0.2945)
MVP		0.59
MPC		0.19
ClinPred		1.0	D
GERP RS		1.9
Varity_R		0.65
gMVP		0.71
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

hg19: chr20-1616887;