19-19629977-C-T

Variant names:

• chr19-19629977-C-T
• rs151053786
• NM_016573.4:c.2899G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016573.4(GMIP):​c.2899G>A​(p.Glu967Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000261 in 1,608,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: GMIP NM_016573.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.40
• Publications: 2 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10396734).

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.2899G>A	p.Glu967Lys	missense	Exon 21 of 21	NP_057657.2	Q9P107-1
	GMIP	NM_001288999.2		c.2821G>A	p.Glu941Lys	missense	Exon 20 of 20	NP_001275928.1	Q9P107-2
	GMIP	NM_001288998.2		c.2812G>A	p.Glu938Lys	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.2899G>A	p.Glu967Lys	missense	Exon 21 of 21	ENSP00000203556.3	Q9P107-1
	GMIP	ENST00000587238.5	TSL:1	c.2821G>A	p.Glu941Lys	missense	Exon 20 of 20	ENSP00000467054.1	Q9P107-2
	GMIP	ENST00000940889.1		c.2875G>A	p.Glu959Lys	missense	Exon 21 of 21	ENSP00000610948.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152158 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000546 AC: 13 AN: 238138 AF XY: 0.0000928

Gnomad AFR exome AF: 0.000202

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000562

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000278

Gnomad OTH exome AF: 0.000173

GnomAD4 exome AF: 0.0000240 AC: 35 AN: 1456582 Hom.: 0 Cov.: 33 AF XY: 0.0000304 AC XY: 22 AN XY: 724098

African (AFR) AF: 0.0000897 AC: 3 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 43832

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25904

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39572

South Asian (SAS) AF: 0.000129 AC: 11 AN: 85080

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52588

Middle Eastern (MID) AF: 0.000523 AC: 3 AN: 5734

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1110224

Other (OTH) AF: 0.0000332 AC: 2 AN: 60198

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152276 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74442

African (AFR) AF: 0.0000962 AC: 4 AN: 41566

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000189 Hom.: 0

Bravo AF: 0.0000529

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000494 AC: 6

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0092	T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.4
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.23
MVP		0.50
MPC		0.57
ClinPred		0.16	T
GERP RS		3.6
Varity_R		0.080
gMVP		0.47
Mutation Taster		=94/6	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: rs151053786; hg19: chr19-19740786; COSMIC: COSV108747642; COSMIC: COSV108747642;