19-19630090-G-C

Variant names:

• chr19-19630090-G-C
• rs994295052
• NM_016573.4:c.2786C>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.2786C>G​(p.Pro929Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,570 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: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: GMIP NM_016573.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

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=0.1870543).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GMIP	NM_016573.4	c.2786C>G	p.Pro929Arg	missense_variant	Exon 21 of 21	ENST00000203556.9	NP_057657.2
GMIP	NM_001288999.2	c.2708C>G	p.Pro903Arg	missense_variant	Exon 20 of 20		NP_001275928.1
GMIP	NM_001288998.2	c.2699C>G	p.Pro900Arg	missense_variant	Exon 20 of 20		NP_001275927.1
GMIP	XM_005259927.3	c.2777C>G	p.Pro926Arg	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.2786C>G	p.Pro929Arg	missense_variant	Exon 21 of 21	1	NM_016573.4	ENSP00000203556.3
GMIP	ENST00000587238.5	c.2708C>G	p.Pro903Arg	missense_variant	Exon 20 of 20	1		ENSP00000467054.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000125 AC: 3 AN: 239272 Hom.: 0 AF XY: 0.0000153 AC XY: 2 AN XY: 130626

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000890

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458570 Hom.: 0 Cov.: 33 AF XY: 0.00000276 AC XY: 2 AN XY: 725402

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000679

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: 0.00

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	Benign	0.078
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.090	N;.
REVEL	Benign	0.037
Sift	Benign	0.037	D;.
Sift4G	Uncertain	0.049	D;D
Polyphen		0.87	P;.
Vest4		0.17
MutPred		0.24		Gain of MoRF binding (P = 0.0091);.;
MVP		0.51
MPC		0.57
ClinPred		0.25	T
GERP RS		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.026
gMVP		0.18

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: rs994295052; hg19: chr19-19740899;