NM_020999.4:c.605G>A

Variant names:

• chr10-69572439-C-T
• rs1318653780
• NM_020999.4:c.605G>A

Variant summary

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

The NM_020999.4(NEUROG3):​c.605G>A​(p.Cys202Tyr) 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. 15/21 in silico tools predict 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NEUROG3 NM_020999.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137

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 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=0.09887475).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEUROG3	NM_020999.4	c.605G>A	p.Cys202Tyr	missense_variant	Exon 2 of 2	ENST00000242462.5	NP_066279.2
NEUROG3	XM_017016280.2	c.605G>A	p.Cys202Tyr	missense_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.605G>A	p.Cys202Tyr	missense_variant	Exon 2 of 2	1	NM_020999.4	ENSP00000242462.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1437194 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 713964

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	6.6
DANN	Benign	0.79
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	0.63	N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.18
Sift	Benign	0.11	T
Sift4G	Benign	0.22	T
Polyphen		0.0020	B
Vest4		0.094
MutPred		0.25		Gain of phosphorylation at C202 (P = 0.1076);
MVP		0.85
MPC		0.69
ClinPred		0.077	T
GERP RS		0.51
Varity_R		0.095
gMVP		0.64

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: rs1318653780; hg19: chr10-71332195;