rs777635375

Variant names:

• chr10-5651228-C-G
• rs777635375
• NM_024701.4:c.367G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-5651228-C-G
• chr10-5651228-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024701.4(ASB13):​c.367G>C​(p.Glu123Gln) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E123K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ASB13 NM_024701.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.68
• Publications: 0 publications found

Genes affected

ASB13 (HGNC:19765): (ankyrin repeat and SOCS box containing 13) 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 a 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, both protein-coding and not protein-coding, have been described for this gene. [provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024701.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB13	NM_024701.4	MANE Select	c.367G>C	p.Glu123Gln	missense	Exon 3 of 6	NP_078977.2
	ASB13	NR_037164.2		n.411G>C		non_coding_transcript_exon	Exon 3 of 7
	ASB13	NR_024581.2		n.275+1635G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB13	ENST00000357700.11	TSL:1 MANE Select	c.367G>C	p.Glu123Gln	missense	Exon 3 of 6	ENSP00000350331.6	Q8WXK3-1
	ASB13	ENST00000459912.5	TSL:1	n.367G>C		non_coding_transcript_exon	Exon 3 of 7	ENSP00000433358.1	Q8WXK3-2
	ASB13	ENST00000904595.1		c.367G>C	p.Glu123Gln	missense	Exon 3 of 5	ENSP00000574654.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000812 AC: 2 AN: 246414 AF XY: 0.0000150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000111

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.1	L
PhyloP100		5.7
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.072	T
Polyphen		0.90	P
Vest4		0.83
MutPred		0.39		Loss of disorder (P = 0.1114)
MVP		0.56
MPC		0.58
ClinPred		0.98	D
GERP RS		3.9
Varity_R		0.81
gMVP		0.56
Mutation Taster		=42/58	disease causing

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

Other links and lift over

dbSNP: rs777635375; hg19: chr10-5693191;