Variant 10-124834636-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032182.4(ABRAXAS2):c.913C>T(p.Pro305Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000112 in 1,613,990 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 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

ABRAXAS2
NM_032182.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.75

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34688306).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABRAXAS2	NM_032182.4 linkuse as main transcript	c.913C>T	p.Pro305Ser	missense_variant	9/9	ENST00000298492.6	NP_115558.3	Q15018
ABRAXAS2	XM_047424888.1 linkuse as main transcript	c.601C>T	p.Pro201Ser	missense_variant	8/8		XP_047280844.1
ABRAXAS2	XM_047424889.1 linkuse as main transcript	c.601C>T	p.Pro201Ser	missense_variant	6/6		XP_047280845.1
ABRAXAS2	XM_047424891.1 linkuse as main transcript	c.601C>T	p.Pro201Ser	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.913C>T	p.Pro305Ser	missense_variant	9/9	1	NM_032182.4	ENSP00000298492.5		Q15018

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000517

AC:

AN:

251340

Hom.:

AF XY:

0.0000663

AC XY:

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000968

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000116

AC:

170

AN:

1461886

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.000139

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000987

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.0000593

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

Jan 18, 2023

The c.913C>T (p.P305S) 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 913, causing the proline (P) at amino acid position 305 to be replaced by a serine (S). 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

0.22

BayesDel_addAF

Benign

-0.064

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.075

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.058

MetaRNN

Benign

0.35

MetaSVM

Benign

-0.34

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.1

REVEL

Benign

0.27

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.055

Polyphen

1.0

Vest4

0.43

MVP

0.81

MPC

1.0

ClinPred

0.33

GERP RS

6.0

Varity_R

0.16

gMVP

0.56

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