10-69572462-C-A

Variant names:

• chr10-69572462-C-A
• rs748454016
• NM_020999.4:c.582G>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS1

The NM_020999.4(NEUROG3):​c.582G>T​(p.Leu194Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,589,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000039 (0 hom.)
• Consequence: NEUROG3 NM_020999.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.577
• Publications: 1 publications found

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]

NEUROG3 Gene-Disease associations (from GenCC):

• congenital malabsorptive diarrhea 4

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• permanent neonatal diabetes mellitus

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp

ENSG00000236154 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 10-69572462-C-A is Benign according to our data. Variant chr10-69572462-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1535174.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.577 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.000039 (56/1436916) while in subpopulation AMR AF = 0.00128 (53/41432). AF 95% confidence interval is 0.001. There are 0 homozygotes in GnomAdExome4. There are 24 alleles in the male GnomAdExome4 subpopulation. Median coverage is 37. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020999.4. 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
	NEUROG3	NM_020999.4	MANE Select	c.582G>T	p.Leu194Leu	synonymous	Exon 2 of 2	NP_066279.2	Q9Y4Z2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEUROG3	ENST00000242462.5	TSL:1 MANE Select	c.582G>T	p.Leu194Leu	synonymous	Exon 2 of 2	ENSP00000242462.4	Q9Y4Z2
	NEUROG3	ENST00000929784.1		c.582G>T	p.Leu194Leu	synonymous	Exon 2 of 2	ENSP00000599843.1
	ENSG00000236154	ENST00000839697.1		n.352C>A		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152188 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000250 AC: 50 AN: 200226 AF XY: 0.000190

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00162

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.0000390 AC: 56 AN: 1436916 Hom.: 0 Cov.: 37 AF XY: 0.0000336 AC XY: 24 AN XY: 713370

African (AFR) AF: 0.00 AC: 0 AN: 32824

American (AMR) AF: 0.00128 AC: 53 AN: 41432

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25742

East Asian (EAS) AF: 0.00 AC: 0 AN: 38336

South Asian (SAS) AF: 0.00 AC: 0 AN: 83822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5622

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101290

Other (OTH) AF: 0.0000505 AC: 3 AN: 59376

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152188 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74350

African (AFR) AF: 0.00 AC: 0 AN: 41462

American (AMR) AF: 0.000196 AC: 3 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000110

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.27
DANN	Benign	0.55
PhyloP100		-0.58
Mutation Taster		=100/0	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: rs748454016; hg19: chr10-71332218;