rs1269114470

Variant names:

• chr10-69572450-G-A
• rs1269114470
• NM_020999.4:c.594C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-69572450-G-A
• chr10-69572450-G-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_020999.4(NEUROG3):​c.594C>T​(p.Thr198Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,437,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NEUROG3 NM_020999.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.471

Genes affected

NEUROG3 (HGNC:13806): (neurogenin 3) The protein encoded by this gene is a basic helix-loop-helix (bHLH) transcription factor involved in neurogenesis. The encoded protein likely acts as a heterodimer with another bHLH protein. Defects in this gene are a cause of congenital malabsorptive diarrhea 4 (DIAR4).[provided by RefSeq, May 2010]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=-0.471 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEUROG3	NM_020999.4	c.594C>T	p.Thr198Thr	synonymous_variant	Exon 2 of 2	ENST00000242462.5	NP_066279.2
NEUROG3	XM_017016280.2	c.594C>T	p.Thr198Thr	synonymous_variant	Exon 2 of 2		XP_016871769.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEUROG3	ENST00000242462.5	c.594C>T	p.Thr198Thr	synonymous_variant	Exon 2 of 2	1	NM_020999.4	ENSP00000242462.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000490 AC: 1 AN: 204052 Hom.: 0 AF XY: 0.00000888 AC XY: 1 AN XY: 112574

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000324

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1437076 Hom.: 0 Cov.: 37 AF XY: 0.00000280 AC XY: 2 AN XY: 713678

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000239

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000119

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.7
DANN	Benign	0.75

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

LitVar

Other links and lift over

dbSNP: rs1269114470; hg19: chr10-71332206;