4-176222326-T-A

Variant names:

• chr4-176222326-T-A
• NM_080874.4:c.371A>T

Variant summary

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

The NM_080874.4(ASB5):​c.371A>T​(p.Glu124Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ASB5 NM_080874.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.87

Genes affected

ASB5 (HGNC:17180): (ankyrin repeat and SOCS box containing 5) The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. They contain ankyrin repeat sequence and SOCS box domain. The SOCS box serves to couple suppressor of cytokine signalling (SOCS) proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. Multiple alternatively spliced transcript variants have been described for this gene but their full length sequences are not known. [provided by RefSeq, Jul 2008]

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
ASB5	NM_080874.4	c.371A>T	p.Glu124Val	missense_variant	Exon 3 of 7	ENST00000296525.7	NP_543150.1
ASB5	NM_001410863.1	c.236A>T	p.Glu79Val	missense_variant	Exon 3 of 7		NP_001397792.1
ASB5	XM_005262759.2	c.371A>T	p.Glu124Val	missense_variant	Exon 5 of 9		XP_005262816.1
ASB5	XM_011531617.4	c.212A>T	p.Glu71Val	missense_variant	Exon 3 of 7		XP_011529919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB5	ENST00000296525.7	c.371A>T	p.Glu124Val	missense_variant	Exon 3 of 7	1	NM_080874.4	ENSP00000296525.3
ASB5	ENST00000672074.1	c.236A>T	p.Glu79Val	missense_variant	Exon 3 of 7			ENSP00000500617.1
ASB5	ENST00000512254.1	c.212A>T	p.Glu71Val	missense_variant	Exon 3 of 7	2		ENSP00000422877.1
ASB5	ENST00000511879.1	n.456A>T		non_coding_transcript_exon_variant	Exon 3 of 4	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.371A>T (p.E124V) alteration is located in exon 3 (coding exon 3) of the ASB5 gene. This alteration results from a A to T substitution at nucleotide position 371, causing the glutamic acid (E) at amino acid position 124 to be replaced by a valine (V). 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	Uncertain	0.34
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.19	T;.
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-4.1	D;D
REVEL	Benign	0.26
Sift	Uncertain	0.016	D;D
Sift4G	Benign	0.092	T;T
Polyphen		0.062	B;.
Vest4		0.56
MutPred		0.49		Gain of catalytic residue at E124 (P = 0.0491);.;
MVP		0.81
MPC		0.22
ClinPred		0.98	D
GERP RS		5.6
Varity_R		0.29
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr4-177143477;