1-75932113-A-G

Position:

• chr1-75932113-A-G

Variant summary

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

The ENST00000284142.7(ASB17):​c.179T>C​(p.Leu60Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ASB17 ENST00000284142.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.32

Genes affected

ASB17 (HGNC:19769): (ankyrin repeat and SOCS box containing 17) Predicted to be involved in intracellular signal transduction and protein ubiquitination. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

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/exons	MANE	Protein	UniProt
ASB17	NM_080868.3	c.179T>C	p.Leu60Ser	missense_variant	1/3	ENST00000284142.7	NP_543144.1
ASB17	XM_047445206.1	c.167+12T>C		intron_variant			XP_047301162.1
ASB17	NR_026546.3	n.292T>C		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASB17	ENST00000284142.7	c.179T>C	p.Leu60Ser	missense_variant	1/3	1	NM_080868.3	ENSP00000284142	P1
	ENST00000663316.1	n.66-2321A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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

Oct 13, 2023

The c.179T>C (p.L60S) alteration is located in exon 1 (coding exon 1) of the ASB17 gene. This alteration results from a T to C substitution at nucleotide position 179, causing the leucine (L) at amino acid position 60 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	0.33
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.90	L
MutationTaster	Benign	0.90	D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.14	N
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.62
MutPred		0.37		Gain of relative solvent accessibility (P = 0.0027);
MVP		0.68
MPC		0.17
ClinPred		0.91	D
GERP RS		6.1
Varity_R		0.17
gMVP		0.27

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: chr1-76397798;