19-19630276-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016573.4(GMIP):​c.2600G>C​(p.Arg867Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R867H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000086 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GMIP NM_016573.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.77
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04109022).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016573.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GMIP	NM_016573.4	MANE Select	c.2600G>C	p.Arg867Pro	missense	Exon 21 of 21	NP_057657.2	Q9P107-1
	GMIP	NM_001288999.2		c.2522G>C	p.Arg841Pro	missense	Exon 20 of 20	NP_001275928.1	Q9P107-2
	GMIP	NM_001288998.2		c.2513G>C	p.Arg838Pro	missense	Exon 20 of 20	NP_001275927.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GMIP	ENST00000203556.9	TSL:1 MANE Select	c.2600G>C	p.Arg867Pro	missense	Exon 21 of 21	ENSP00000203556.3	Q9P107-1
	GMIP	ENST00000587238.5	TSL:1	c.2522G>C	p.Arg841Pro	missense	Exon 20 of 20	ENSP00000467054.1	Q9P107-2
	GMIP	ENST00000940889.1		c.2576G>C	p.Arg859Pro	missense	Exon 21 of 21	ENSP00000610948.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000623 AC: 12 AN: 192624 AF XY: 0.0000385

Gnomad AFR exome AF: 0.000284

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000555

Gnomad NFE exome AF: 0.0000801

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000859 AC: 12 AN: 1396590 Hom.: 0 Cov.: 33 AF XY: 0.0000116 AC XY: 8 AN XY: 687268

African (AFR) AF: 0.00 AC: 0 AN: 31742

American (AMR) AF: 0.00 AC: 0 AN: 36780

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21844

East Asian (EAS) AF: 0.00 AC: 0 AN: 39016

South Asian (SAS) AF: 0.00 AC: 0 AN: 76438

European-Finnish (FIN) AF: 0.000242 AC: 12 AN: 49574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5448

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078400

Other (OTH) AF: 0.00 AC: 0 AN: 57348

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.000387 AC: 46

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.054	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		5.8
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.30
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.41
MVP		0.59
MPC		1.2
ClinPred		0.087	T
GERP RS		4.3
Varity_R		0.43
gMVP		0.57
Mutation Taster		=52/48	polymorphism

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

Other links and lift over

dbSNP: rs199807296; hg19: chr19-19741085; COSMIC: COSV52560293; COSMIC: COSV52560293;