chr19-19633864-G-T

Variant names:

• chr19-19633864-G-T
• rs757839419
• NM_016573.4:c.2411C>A

Variant summary

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

The NM_016573.4(GMIP):​c.2411C>A​(p.Pro804His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000742 in 1,348,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 30)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: GMIP NM_016573.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.240

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=0.09909451).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GMIP	NM_016573.4	c.2411C>A	p.Pro804His	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.2411C>A	p.Pro804His	missense_variant	Exon 19 of 21	1	NM_016573.4	ENSP00000203556.3
GMIP	ENST00000587238.5	c.2333C>A	p.Pro778His	missense_variant	Exon 18 of 20	1		ENSP00000467054.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD3 exomes AF: 0.00000666 AC: 1 AN: 150124 Hom.: 0 AF XY: 0.0000126 AC XY: 1 AN XY: 79608

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: 0.0000140

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.42e-7 AC: 1 AN: 1348004 Hom.: 0 Cov.: 32 AF XY: 0.00000152 AC XY: 1 AN XY: 658278

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: 9.46e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ExAC AF: 0.0000170 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.4
DANN	Benign	0.73
DEOGEN2	Benign	0.022	T;.
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.61	T;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.099	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.91	N;.
REVEL	Benign	0.013
Sift	Benign	0.14	T;.
Sift4G	Benign	0.11	T;T
Polyphen		0.64	P;.
Vest4		0.21
MutPred		0.20		Gain of solvent accessibility (P = 0.0704);.;
MVP		0.36
MPC		0.62
ClinPred		0.075	T
GERP RS		0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.038
gMVP		0.14

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: rs757839419; hg19: chr19-19744673;