5-135535483-C-T

Position:

• chr5-135535483-C-T

Variant summary

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

The NM_006161.3(NEUROG1):​c.208G>A​(p.Glu70Lys) 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: 33)
• Consequence: NEUROG1 NM_006161.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.03

Genes affected

NEUROG1 (HGNC:7764): (neurogenin 1) Enables E-box binding activity and protein homodimerization activity. Involved in several processes, including animal organ morphogenesis; cranial nerve development; and hard palate morphogenesis. Predicted to be located in neuronal cell body. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000250167 (HGNC:):

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=0.14442152).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEUROG1	NM_006161.3	c.208G>A	p.Glu70Lys	missense_variant	1/1	ENST00000314744.6	NP_006152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEUROG1	ENST00000314744.6	c.208G>A	p.Glu70Lys	missense_variant	1/1	6	NM_006161.3	ENSP00000317580.4
ENSG00000250167	ENST00000698884.1	n.496+48714C>T		intron_variant
SLC25A48	ENST00000698885.1	n.364+25727C>T		intron_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Dec 16, 2021

The c.208G>A (p.E70K) alteration is located in exon 1 (coding exon 1) of the NEUROG1 gene. This alteration results from a G to A substitution at nucleotide position 208, causing the glutamic acid (E) at amino acid position 70 to be replaced by a lysine (K). 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
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.63	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.14	T
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Benign	1.8	L
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	0.11	N
REVEL	Benign	0.17
Sift	Benign	0.39	T
Sift4G	Benign	0.80	T
Polyphen		0.0010	B
Vest4		0.18
MutPred		0.29		Gain of MoRF binding (P = 0.0152);
MVP		0.89
MPC		0.72
ClinPred		0.39	T
GERP RS		2.8
Varity_R		0.14
gMVP		0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-134871173;