Variant 10-124829436-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032182.4(ABRAXAS2):c.622G>A(p.Ala208Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,286 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ABRAXAS2
NM_032182.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.57

Variant links:

Genes affected

ABRAXAS2 (HGNC:28975): (abraxas 2, BRISC complex subunit) Enables microtubule binding activity and polyubiquitin modification-dependent protein binding activity. Involved in several processes, including mitotic spindle assembly; protein K63-linked deubiquitination; and response to ischemia. Located in cytoplasm. Part of BRISC complex. Colocalizes with microtubule minus-end; midbody; and spindle pole centrosome. [provided by Alliance of Genome Resources, Apr 2022]

ABRAXAS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06549001).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABRAXAS2	NM_032182.4 linkuse as main transcript	c.622G>A	p.Ala208Thr	missense_variant	7/9	ENST00000298492.6	NP_115558.3	Q15018
ABRAXAS2	XM_047424888.1 linkuse as main transcript	c.310G>A	p.Ala104Thr	missense_variant	6/8		XP_047280844.1
ABRAXAS2	XM_047424889.1 linkuse as main transcript	c.310G>A	p.Ala104Thr	missense_variant	4/6		XP_047280845.1
ABRAXAS2	XM_047424891.1 linkuse as main transcript	c.310G>A	p.Ala104Thr	missense_variant	4/6		XP_047280847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABRAXAS2	ENST00000298492.6 linkuse as main transcript	c.622G>A	p.Ala208Thr	missense_variant	7/9	1	NM_032182.4	ENSP00000298492.5		Q15018

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249506

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134992

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1458820

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725776

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

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 submitter

clinical testing

Ambry Genetics

Dec 04, 2023

The c.622G>A (p.A208T) alteration is located in exon 7 (coding exon 7) of the FAM175B gene. This alteration results from a G to A substitution at nucleotide position 622, causing the alanine (A) at amino acid position 208 to be replaced by a threonine (T). 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

0.13

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.037

Eigen

Benign

-0.031

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0082

MetaRNN

Benign

0.065

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.45

REVEL

Benign

0.031

Sift

Benign

0.31

Sift4G

Benign

0.68

Polyphen

0.075

Vest4

0.079

MutPred

0.25

Gain of phosphorylation at A208 (P = 0.1094);

MVP

0.52

MPC

0.37

ClinPred

0.31

GERP RS

5.8

Varity_R

0.24

gMVP

0.082

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over