17-29575675-G-C

Position:

• chr17-29575675-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_014030.4(GIT1):​c.1781C>G​(p.Ala594Gly) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 33)
• Consequence: GIT1 NM_014030.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.23

Genes affected

GIT1 (HGNC:4272): (GIT ArfGAP 1) Enables gamma-tubulin binding activity. Involved in positive regulation of microtubule nucleation and regulation of cytokinesis. Located in several cellular components, including focal adhesion; microtubule cytoskeleton; and mitochondrion. Implicated in attention deficit hyperactivity disorder. Biomarker of Huntington's disease. [provided by Alliance of Genome Resources, Apr 2022]

ABHD15-AS1 (HGNC:49685): (ABHD15 antisense RNA 1)

TP53I13 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, GIT1
• BP4: Computational evidence support a benign effect (MetaRNN=0.23773313).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GIT1	NM_014030.4	c.1781C>G	p.Ala594Gly	missense_variant	17/20	ENST00000225394.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GIT1	ENST00000225394.8	c.1781C>G	p.Ala594Gly	missense_variant	17/20	1	NM_014030.4	A1
ABHD15-AS1	ENST00000581474.1	n.153+14976G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;.;.;.;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.061
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D;D;D;D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.24	T;T;T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	0.34	N;.;.;.;.
MutationTaster	Benign	0.74	D;D;D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.1	N;N;.;.;.
REVEL	Benign	0.10
Sift	Benign	0.17	T;T;.;.;.
Sift4G	Benign	0.36	T;T;T;T;T
Polyphen		0.023	B;B;.;.;.
Vest4		0.11
MutPred		0.24		Gain of helix (P = 0.0496);.;.;Gain of helix (P = 0.0496);.;
MVP		0.51
MPC		1.1
ClinPred		0.65	D
GERP RS		5.4
Varity_R		0.098
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-27902693;