19-19630070-T-A

Position:

• chr19-19630070-T-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.2806A>T​(p.Ile936Phe) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GMIP NM_016573.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.18

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=0.24823862).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GMIP	NM_016573.4	c.2806A>T	p.Ile936Phe	missense_variant	21/21	ENST00000203556.9
GMIP	NM_001288999.2	c.2728A>T	p.Ile910Phe	missense_variant	20/20
GMIP	NM_001288998.2	c.2719A>T	p.Ile907Phe	missense_variant	20/20
GMIP	XM_005259927.3	c.2797A>T	p.Ile933Phe	missense_variant	21/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GMIP	ENST00000203556.9	c.2806A>T	p.Ile936Phe	missense_variant	21/21	1	NM_016573.4	P1
GMIP	ENST00000587238.5	c.2728A>T	p.Ile910Phe	missense_variant	20/20	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 31, 2023

The c.2806A>T (p.I936F) alteration is located in exon 21 (coding exon 21) of the GMIP gene. This alteration results from a A to T substitution at nucleotide position 2806, causing the isoleucine (I) at amino acid position 936 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	2.0	M;.
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.5	N;.
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.33
MutPred		0.14		Gain of ubiquitination at K932 (P = 0.154);.;
MVP		0.55
MPC		1.1
ClinPred		0.90	D
GERP RS		5.1
Varity_R		0.28
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-19740879;