chr19-19630325-C-G

Variant names:

• chr19-19630325-C-G
• rs367825362
• NM_016573.4:c.2551G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016573.4(GMIP):​c.2551G>C​(p.Gly851Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000274 in 1,386,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 32)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: GMIP NM_016573.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.653

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 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=0.041868806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GMIP	NM_016573.4	c.2551G>C	p.Gly851Arg	missense_variant	Exon 21 of 21	ENST00000203556.9	NP_057657.2
GMIP	NM_001288999.2	c.2473G>C	p.Gly825Arg	missense_variant	Exon 20 of 20		NP_001275928.1
GMIP	NM_001288998.2	c.2464G>C	p.Gly822Arg	missense_variant	Exon 20 of 20		NP_001275927.1
GMIP	XM_005259927.3	c.2542G>C	p.Gly848Arg	missense_variant	Exon 21 of 21		XP_005259984.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GMIP	ENST00000203556.9	c.2551G>C	p.Gly851Arg	missense_variant	Exon 21 of 21	1	NM_016573.4	ENSP00000203556.3
GMIP	ENST00000587238.5	c.2473G>C	p.Gly825Arg	missense_variant	Exon 20 of 20	1		ENSP00000467054.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000527 AC: 1 AN: 189794 Hom.: 0 AF XY: 0.00000995 AC XY: 1 AN XY: 100472

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: 0.0000113

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000274 AC: 38 AN: 1386920 Hom.: 0 Cov.: 33 AF XY: 0.0000264 AC XY: 18 AN XY: 681414

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: 0.0000335

Gnomad4 OTH exome AF: 0.0000350

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000829 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Benign	0.86
DEOGEN2	Benign	0.018	T;.
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.20	N
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.042	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.48	N;.
REVEL	Benign	0.040
Sift	Benign	0.43	T;.
Sift4G	Benign	0.12	T;T
Polyphen		0.78	P;.
Vest4		0.073
MutPred		0.11		Gain of solvent accessibility (P = 0.0456);.;
MVP		0.37
MPC		0.33
ClinPred		0.11	T
GERP RS		3.1
Varity_R		0.035
gMVP		0.22

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: rs367825362; hg19: chr19-19741134;