17-1006153-T-A

Position:

• chr17-1006153-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021962.5(ABR):​c.2507A>T​(p.Tyr836Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ABR NM_021962.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.95

Genes affected

ABR (HGNC:81): (ABR activator of RhoGEF and GTPase) This gene encodes a protein that is similar to the protein encoded by the breakpoint cluster region gene located on chromosome 22. The protein encoded by this gene contains a GTPase-activating protein domain, a domain found in members of the Rho family of GTP-binding proteins. Functional studies in mice determined that this protein plays a role in vestibular morphogenesis. Alternatively spliced transcript variants have been reported for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABR	NM_021962.5	c.2507A>T	p.Tyr836Phe	missense_variant	23/23	ENST00000302538.10	NP_068781.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABR	ENST00000302538.10	c.2507A>T	p.Tyr836Phe	missense_variant	23/23	1	NM_021962.5	ENSP00000303909.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Aug 01, 2022

The c.2507A>T (p.Y836F) alteration is located in exon 23 (coding exon 23) of the ABR gene. This alteration results from a A to T substitution at nucleotide position 2507, causing the tyrosine (Y) at amino acid position 836 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	Benign	0.26
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	26
DANN	Benign	0.97
DEOGEN2	Benign	0.16	T;.;.;.;.;T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	.;.;D;.;.;.
M_CAP	Benign	0.0083	T
MetaRNN	Uncertain	0.54	D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.78	N;.;.;.;.;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.4	N;N;.;N;D;N
REVEL	Benign	0.26
Sift	Uncertain	0.013	D;D;.;D;T;D
Sift4G	Benign	0.17	T;T;.;T;T;T
Polyphen		0.60	P;.;.;D;.;B
Vest4		0.62
MutPred		0.57		Gain of helix (P = 0.0425);.;.;.;.;.;
MVP		0.55
MPC		2.0
ClinPred		0.78	D
GERP RS		5.6
Varity_R		0.47
gMVP		0.62

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: chr17-909393;