rs199807296

Variant names:

• chr19-19630276-C-A
• rs199807296
• NM_016573.4:c.2600G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-19630276-C-A
• chr19-19630276-C-G
• chr19-19630276-C-T

Variant summary

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

The NM_016573.4(GMIP):​c.2600G>T​(p.Arg867Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000716 in 1,396,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 7.2e-7 (0 hom.)
• Consequence: GMIP NM_016573.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.77

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=0.22015777).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GMIP	NM_016573.4	c.2600G>T	p.Arg867Leu	missense_variant	Exon 21 of 21	ENST00000203556.9	NP_057657.2
GMIP	NM_001288999.2	c.2522G>T	p.Arg841Leu	missense_variant	Exon 20 of 20		NP_001275928.1
GMIP	NM_001288998.2	c.2513G>T	p.Arg838Leu	missense_variant	Exon 20 of 20		NP_001275927.1
GMIP	XM_005259927.3	c.2591G>T	p.Arg864Leu	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.2600G>T	p.Arg867Leu	missense_variant	Exon 21 of 21	1	NM_016573.4	ENSP00000203556.3
GMIP	ENST00000587238.5	c.2522G>T	p.Arg841Leu	missense_variant	Exon 20 of 20	1		ENSP00000467054.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1396590 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 687268

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: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.073	T;.
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.8	D;.
REVEL	Benign	0.26
Sift	Uncertain	0.0020	D;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.41
MutPred		0.34		Loss of MoRF binding (P = 0.0067);.;
MVP		0.52
MPC		1.1
ClinPred		0.96	D
GERP RS		4.3
Varity_R		0.28
gMVP		0.55

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: rs199807296; hg19: chr19-19741085;