10-124834823-A-C

Position:

• chr10-124834823-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032182.4(ABRAXAS2):​c.1100A>C​(p.Asp367Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABRAXAS2 NM_032182.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.51

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25500655).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABRAXAS2	NM_032182.4	c.1100A>C	p.Asp367Ala	missense_variant	9/9	ENST00000298492.6	NP_115558.3
ABRAXAS2	XM_047424888.1	c.788A>C	p.Asp263Ala	missense_variant	8/8		XP_047280844.1
ABRAXAS2	XM_047424889.1	c.788A>C	p.Asp263Ala	missense_variant	6/6		XP_047280845.1
ABRAXAS2	XM_047424891.1	c.788A>C	p.Asp263Ala	missense_variant	6/6		XP_047280847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABRAXAS2	ENST00000298492.6	c.1100A>C	p.Asp367Ala	missense_variant	9/9	1	NM_032182.4	ENSP00000298492.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2023

The c.1100A>C (p.D367A) alteration is located in exon 9 (coding exon 9) of the FAM175B gene. This alteration results from a A to C substitution at nucleotide position 1100, causing the aspartic acid (D) at amino acid position 367 to be replaced by an alanine (A). 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	0.093
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.074	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.62	T
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.022	D
Polyphen		0.93	P
Vest4		0.35
MutPred		0.072		Loss of helix (P = 0.028);
MVP		0.71
MPC		1.1
ClinPred		0.93	D
GERP RS		5.5
Varity_R		0.25
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-126523392;