chr5-135535519-C-A

Variant names:

• chr5-135535519-C-A
• NM_006161.3:c.172G>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.172G>T​(p.Ala58Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,423,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 7.0e-7 (0 hom.)
• Consequence: NEUROG1 NM_006161.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.702

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:):

SLC25A48 (HGNC:30451): (solute carrier family 25 member 48) Predicted to enable acyl carnitine transmembrane transporter activity. Predicted to be involved in acyl carnitine transport and amino acid transport. Predicted to be located in mitochondrial inner membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.123991996).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEUROG1	NM_006161.3	c.172G>T	p.Ala58Ser	missense_variant	Exon 1 of 1	ENST00000314744.6	NP_006152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEUROG1	ENST00000314744.6	c.172G>T	p.Ala58Ser	missense_variant	Exon 1 of 1	6	NM_006161.3	ENSP00000317580.4
ENSG00000250167	ENST00000698884.1	n.496+48750C>A		intron_variant	Intron 3 of 5
SLC25A48	ENST00000698885.1	n.364+25763C>A		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1423522 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 706576

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: 0.0000169

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.172G>T (p.A58S) alteration is located in exon 1 (coding exon 1) of the NEUROG1 gene. This alteration results from a G to T substitution at nucleotide position 172, causing the alanine (A) at amino acid position 58 to be replaced by a serine (S). 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	0.077
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	3.5
DANN	Benign	0.70
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.38	T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	1.4	L
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.15
Sift	Benign	0.13	T
Sift4G	Benign	0.50	T
Polyphen		0.018	B
Vest4		0.12
MutPred		0.32		Gain of phosphorylation at A58 (P = 0.0082);
MVP		0.45
MPC		0.44
ClinPred		0.070	T
GERP RS		3.9
Varity_R		0.060
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr5-134871209;