19-19633953-G-C

Variant names:

• chr19-19633953-G-C
• rs141571813
• NM_016573.4:c.2322C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016573.4(GMIP):​c.2322C>G​(p.Ser774Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000698 in 1,433,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: GMIP NM_016573.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.96

Genes affected

GMIP (HGNC:24852): (GEM interacting protein) This gene encodes a member of the ARHGAP family of Rho/Rac/Cdc42-like GTPase activating proteins. The encoded protein interacts with the Ras-related protein Gem through its N-terminal domain. Separately, it interacts with RhoA through a RhoGAP domain, and stimulates RhoA-dependent GTPase activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15944183).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GMIP	NM_016573.4	c.2322C>G	p.Ser774Arg	missense_variant	Exon 19 of 21	ENST00000203556.9	NP_057657.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GMIP	ENST00000203556.9	c.2322C>G	p.Ser774Arg	missense_variant	Exon 19 of 21	1	NM_016573.4	ENSP00000203556.3
GMIP	ENST00000587238.5	c.2244C>G	p.Ser748Arg	missense_variant	Exon 18 of 20	1		ENSP00000467054.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD3 exomes AF: 0.00000423 AC: 1 AN: 236222 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 129030

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000958

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1433554 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 708544

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.16e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.023	T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.3	N;.
REVEL	Benign	0.028
Sift	Benign	0.32	T;.
Sift4G	Benign	0.10	T;T
Polyphen		0.47	P;.
Vest4		0.30
MutPred		0.26		Loss of glycosylation at S774 (P = 0.0018);.;
MVP		0.56
MPC		0.72
ClinPred		0.44	T
GERP RS		3.4
Varity_R		0.058
gMVP		0.28

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: rs141571813; hg19: chr19-19744762;