17-1006153-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

Scores

3
5
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.95
Variant links:
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]

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ACMG classification

Classification made for transcript

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
ABRNM_021962.5 linkc.2507A>T p.Tyr836Phe missense_variant 23/23 ENST00000302538.10 NP_068781.2 Q12979-1Q6ZT60B7Z7Z1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ABRENST00000302538.10 linkc.2507A>T p.Tyr836Phe missense_variant 23/231 NM_021962.5 ENSP00000303909.5 Q12979-1

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
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 01, 2022The 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; API