5-135535147-C-T

Variant names:

• chr5-135535147-C-T
• rs765604357
• NM_006161.3:c.544G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006161.3(NEUROG1):​c.544G>A​(p.Asp182Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D182Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NEUROG1 NM_006161.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.55
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006161.3. 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
	NEUROG1	NM_006161.3	MANE Select	c.544G>A	p.Asp182Asn	missense	Exon 1 of 1	NP_006152.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEUROG1	ENST00000314744.6	TSL:6 MANE Select	c.544G>A	p.Asp182Asn	missense	Exon 1 of 1	ENSP00000317580.4	Q92886
	ENSG00000250167	ENST00000698884.1		n.496+48378C>T		intron	N/A
	SLC25A48	ENST00000698885.1		n.364+25391C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.50	T
Eigen	Benign	0.031
Eigen_PC	Benign	-0.00015
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.74	T
M_CAP	Pathogenic	0.94	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Uncertain	0.60	D
MutationAssessor	Benign	1.9	L
PhyloP100		2.6
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.94	N
REVEL	Uncertain	0.33
Sift	Benign	0.10	T
Sift4G	Benign	0.38	T
Polyphen		1.0	D
Vest4		0.31
MutPred		0.17		Gain of glycosylation at P179 (P = 0.1466)
MVP		0.89
MPC		1.1
ClinPred		0.69	D
GERP RS		4.2
Varity_R		0.10
gMVP		0.70
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

dbSNP: rs765604357; hg19: chr5-134870837;