14-23476107-G-A

Position:

• chr14-23476107-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001042635.2(NGDN):​c.499G>A​(p.Val167Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: NGDN NM_001042635.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.773

Genes affected

NGDN (HGNC:20271): (neuroguidin) Neuroguidin is an EIF4E (MIM 133440)-binding protein that interacts with CPEB (MIM 607342) and functions as a translational regulatory protein during development of the vertebrate nervous system (Jung et al., 2006 [PubMed 16705177]).[supplied by OMIM, Mar 2008]

NGDN (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06320116).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NGDN	NM_001042635.2	c.499G>A	p.Val167Met	missense_variant	7/11	ENST00000408901.8	NP_001036100.1
NGDN	NM_015514.2	c.499G>A	p.Val167Met	missense_variant	7/10		NP_056329.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NGDN	ENST00000408901.8	c.499G>A	p.Val167Met	missense_variant	7/11	1	NM_001042635.2	ENSP00000386134.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461840 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 727218

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: 0.00000630

Gnomad4 OTH exome AF: 0.00

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

Sep 20, 2023

The c.499G>A (p.V167M) alteration is located in exon 7 (coding exon 7) of the NGDN gene. This alteration results from a G to A substitution at nucleotide position 499, causing the valine (V) at amino acid position 167 to be replaced by a methionine (M). 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	0.083
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.5
DANN	Benign	0.95
DEOGEN2	Benign	0.056	T;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.063	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.090	N;N
REVEL	Benign	0.030
Sift	Benign	0.076	T;T
Sift4G	Benign	0.11	T;T
Polyphen		0.19	B;B
Vest4		0.25
MutPred		0.25		Loss of ubiquitination at K162 (P = 0.0877);Loss of ubiquitination at K162 (P = 0.0877);
MVP		0.20
MPC		0.11
ClinPred		0.11	T
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.021
gMVP		0.14

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: chr14-23945316;