chr5-135535473-C-T

Variant names:

• chr5-135535473-C-T
• rs567322906
• NM_006161.3:c.218G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006161.3(NEUROG1):​c.218G>A​(p.Arg73Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000128 in 1,565,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. R73P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: NEUROG1 NM_006161.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.00
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26126704).

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.218G>A	p.Arg73Gln	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.218G>A	p.Arg73Gln	missense	Exon 1 of 1	ENSP00000317580.4	Q92886
	ENSG00000250167	ENST00000698884.1		n.496+48704C>T		intron	N/A
	SLC25A48	ENST00000698885.1		n.364+25717C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152096 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000575 AC: 1 AN: 174064 AF XY: 0.00

Gnomad AFR exome AF: 0.000117

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1412896 Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1 AN XY: 699830

African (AFR) AF: 0.0000321 AC: 1 AN: 31132

American (AMR) AF: 0.00 AC: 0 AN: 38530

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24032

East Asian (EAS) AF: 0.00 AC: 0 AN: 37390

South Asian (SAS) AF: 0.00 AC: 0 AN: 79594

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5586

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1093064

Other (OTH) AF: 0.00 AC: 0 AN: 58406

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152210 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74404

African (AFR) AF: 0.0000241 AC: 1 AN: 41540

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2116

ExAC AF: 0.00000878 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.68	T
M_CAP	Pathogenic	0.46	D
MetaRNN	Benign	0.26	T
MetaSVM	Pathogenic	0.82	D
MutationAssessor	Benign	1.8	L
PhyloP100		4.0
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.47
Sift	Uncertain	0.021	D
Sift4G	Benign	0.077	T
Polyphen		1.0	D
Vest4		0.15
MutPred		0.27		Loss of MoRF binding (P = 0.0739)
MVP		0.88
MPC		1.4
ClinPred		0.46	T
GERP RS		3.7
PromoterAI		-0.012	Neutral
Varity_R		0.27
gMVP		0.63
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

dbSNP: rs567322906; hg19: chr5-134871163; COSMIC: COSV59083351;