12-107775725-G-T

Variant names:

• chr12-107775725-G-T
• rs2136353806
• NM_203436.3:c.507G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_203436.3(ASCL4):​c.507G>T​(p.Glu169Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000158 in 1,263,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: ASCL4 NM_203436.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.657
• Publications: 0 publications found

Genes affected

ASCL4 (HGNC:24311): (achaete-scute family bHLH transcription factor 4) Basic helix-loop-helix transcription factors, such as ASCL4, 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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.084563464).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203436.3. 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
	ASCL4	NM_203436.3	MANE Select	c.507G>T	p.Glu169Asp	missense	Exon 1 of 1	NP_982260.3	Q6XD76

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASCL4	ENST00000342331.5	TSL:6 MANE Select	c.507G>T	p.Glu169Asp	missense	Exon 1 of 1	ENSP00000345420.5	Q6XD76

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000158 AC: 2 AN: 1263808 Hom.: 0 Cov.: 30 AF XY: 0.00000162 AC XY: 1 AN XY: 616068

African (AFR) AF: 0.00 AC: 0 AN: 25482

American (AMR) AF: 0.00 AC: 0 AN: 16636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17908

East Asian (EAS) AF: 0.00 AC: 0 AN: 32580

South Asian (SAS) AF: 0.00 AC: 0 AN: 60644

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35082

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3708

European-Non Finnish (NFE) AF: 0.00000196 AC: 2 AN: 1019662

Other (OTH) AF: 0.00 AC: 0 AN: 52106

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	16
DANN	Uncertain	0.99
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.74	D
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.085	T
MetaSVM	Uncertain	-0.059	T
PhyloP100		0.66
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.19
Sift	Benign	0.13	T
Sift4G	Benign	0.12	T
Vest4		0.14
MVP		0.49
MPC		0.40
ClinPred		0.30	T
GERP RS		1.7
gMVP		0.24
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs2136353806; hg19: chr12-108169502;