11-8938067-T-C

Position:

• chr11-8938067-T-C

Variant summary

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

The NM_020646.3(ASCL3):​c.95A>G​(p.Glu32Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: ASCL3 NM_020646.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.19

Genes affected

ASCL3 (HGNC:740): (achaete-scute family bHLH transcription factor 3) Basic helix-loop-helix transcription factors, such as ASCL3, are essential for the determination of cell fate and the development and differentiation of numerous tissues (Jonsson et al., 2004 [PubMed 15475265]).[supplied by OMIM, Mar 2008]

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=0.22231886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASCL3	NM_020646.3	c.95A>G	p.Glu32Gly	missense_variant	2/2	ENST00000531618.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASCL3	ENST00000531618.2	c.95A>G	p.Glu32Gly	missense_variant	2/2		NM_020646.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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

Aug 22, 2023

The c.95A>G (p.E32G) alteration is located in exon 2 (coding exon 1) of the ASCL3 gene. This alteration results from a A to G substitution at nucleotide position 95, causing the glutamic acid (E) at amino acid position 32 to be replaced by a glycine (G). 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
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Benign	-0.13
Eigen_PC	Benign	0.098
FATHMM_MKL	Uncertain	0.80	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.22	T
MetaSVM	Uncertain	0.41	D
MutationTaster	Benign	0.73	N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.010	N
REVEL	Uncertain	0.29
Sift	Benign	0.15	T
Sift4G	Uncertain	0.031	D
Vest4		0.22
MVP		0.67
ClinPred		0.55	D
GERP RS		5.7
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr11-8959614;