rs567322906

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-135535473-C-A
• chr5-135535473-C-G
• chr5-135535473-C-T

Variant summary

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

The NM_006161.3(NEUROG1):​c.218G>T​(p.Arg73Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000708 in 1,412,896 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (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 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.218G>T	p.Arg73Leu	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>T	p.Arg73Leu	missense	Exon 1 of 1	ENSP00000317580.4	Q92886
	ENSG00000250167	ENST00000698884.1		n.496+48704C>A		intron	N/A
	SLC25A48	ENST00000698885.1		n.364+25717C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 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: 0.0000221 AC: 1 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

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.71	D
Eigen	Benign	0.11
Eigen_PC	Benign	0.091
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.62	T
M_CAP	Pathogenic	0.56	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Uncertain	0.64	D
MutationAssessor	Benign	1.8	L
PhyloP100		4.0
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.039	D
Polyphen		0.96	D
Vest4		0.24
MutPred		0.24		Gain of methylation at R77 (P = 0.0585)
MVP		0.90
MPC		1.4
ClinPred		0.98	D
GERP RS		3.7
PromoterAI		0.0022	Neutral
Varity_R		0.30
gMVP		0.71
Mutation Taster		=57/43	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;