10-124834597-G-T

Variant names:

• chr10-124834597-G-T
• rs1051041
• NM_032182.4:c.874G>T

Variant summary

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

The NM_032182.4(ABRAXAS2):​c.874G>T​(p.Gly292Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABRAXAS2 NM_032182.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.91

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]

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 rank	MANE	Protein	UniProt
ABRAXAS2	NM_032182.4	c.874G>T	p.Gly292Cys	missense_variant	Exon 9 of 9	ENST00000298492.6	NP_115558.3
ABRAXAS2	XM_047424888.1	c.562G>T	p.Gly188Cys	missense_variant	Exon 8 of 8		XP_047280844.1
ABRAXAS2	XM_047424889.1	c.562G>T	p.Gly188Cys	missense_variant	Exon 6 of 6		XP_047280845.1
ABRAXAS2	XM_047424891.1	c.562G>T	p.Gly188Cys	missense_variant	Exon 6 of 6		XP_047280847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABRAXAS2	ENST00000298492.6	c.874G>T	p.Gly292Cys	missense_variant	Exon 9 of 9	1	NM_032182.4	ENSP00000298492.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.73	T
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	0.63	N
REVEL	Benign	0.17
Sift	Benign	0.049	D
Sift4G	Uncertain	0.042	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.23		Loss of methylation at R293 (P = 0.0891);
MVP		0.60
MPC		1.1
ClinPred		0.78	D
GERP RS		5.3
Varity_R		0.14
gMVP		0.22

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

Other links and lift over

dbSNP: rs1051041; hg19: chr10-126523166;