Variant 10-124834574-C-T 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.851C>T(p.Pro284Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000436 in 1,614,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00045 ( 0 hom. )

Consequence

ABRAXAS2
NM_032182.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.15

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:

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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=0.040976137).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABRAXAS2	NM_032182.4 linkuse as main transcript	c.851C>T	p.Pro284Leu	missense_variant	9/9	ENST00000298492.6	NP_115558.3	Q15018
ABRAXAS2	XM_047424888.1 linkuse as main transcript	c.539C>T	p.Pro180Leu	missense_variant	8/8		XP_047280844.1
ABRAXAS2	XM_047424889.1 linkuse as main transcript	c.539C>T	p.Pro180Leu	missense_variant	6/6		XP_047280845.1
ABRAXAS2	XM_047424891.1 linkuse as main transcript	c.539C>T	p.Pro180Leu	missense_variant	6/6		XP_047280847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABRAXAS2	ENST00000298492.6 linkuse as main transcript	c.851C>T	p.Pro284Leu	missense_variant	9/9	1	NM_032182.4	ENSP00000298492.5		Q15018

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000263

AC:

AN:

251176

Hom.:

AF XY:

0.000317

AC XY:

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000476

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000453

AC:

662

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000459

AC XY:

334

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000689

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000558

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000269

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000450

Hom.:

Bravo

AF:

0.000298

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000321

AC:

EpiCase

AF:

0.000654

EpiControl

AF:

0.000711

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

Oct 26, 2021

The c.851C>T (p.P284L) alteration is located in exon 9 (coding exon 9) of the FAM175B gene. This alteration results from a C to T substitution at nucleotide position 851, causing the proline (P) at amino acid position 284 to be replaced by a leucine (L). 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

0.070

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.046

Eigen

Benign

-0.13

Eigen_PC

Benign

0.0059

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.64

M_CAP

Benign

0.014

MetaRNN

Benign

0.041

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.6

REVEL

Benign

0.039

Sift

Benign

0.11

Sift4G

Benign

0.44

Polyphen

0.63

Vest4

0.059

MVP

0.44

MPC

0.37

ClinPred

0.085

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.040

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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