1-15169409-T-G

Variant names:

• chr1-15169409-T-G
• rs7539166
• NM_001136218.2:c.-267+15455T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018022.3(TMEM51):​c.-194+15455T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.94 in 152,060 control chromosomes in the GnomAD database, including 67,225 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.94 (67225 hom., cov: 29)
• Consequence: TMEM51 NM_018022.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344
• Publications: 3 publications found

Genes affected

TMEM51 (HGNC:25488): (transmembrane protein 51) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM51-AS2 (HGNC:32332): (TMEM51 antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018022.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM51	NM_001136218.2	MANE Select	c.-267+15455T>G		intron	N/A	NP_001129690.1
	TMEM51	NM_001136216.2		c.-267+16625T>G		intron	N/A	NP_001129688.1
	TMEM51	NM_001136217.2		c.-194+16625T>G		intron	N/A	NP_001129689.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM51	ENST00000376008.3	TSL:2 MANE Select	c.-267+15455T>G		intron	N/A	ENSP00000365176.1
	TMEM51	ENST00000400796.7	TSL:1	c.-194+15455T>G		intron	N/A	ENSP00000383600.2
	TMEM51	ENST00000434578.6	TSL:1	c.-267+15455T>G		intron	N/A	ENSP00000409665.2

Frequencies

GnomAD3 genomes AF: 0.940 AC: 142830 AN: 151942 Hom.: 67177 Cov.: 29

Gnomad AFR AF: 0.915

Gnomad AMI AF: 0.957

Gnomad AMR AF: 0.961

Gnomad ASJ AF: 0.982

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.988

Gnomad FIN AF: 0.931

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.942

Gnomad OTH AF: 0.947

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.940 AC: 142937 AN: 152060 Hom.: 67225 Cov.: 29 AF XY: 0.942 AC XY: 70013 AN XY: 74308

African (AFR) AF: 0.915 AC: 37928 AN: 41446

American (AMR) AF: 0.961 AC: 14679 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.982 AC: 3411 AN: 3472

East Asian (EAS) AF: 0.989 AC: 5117 AN: 5174

South Asian (SAS) AF: 0.988 AC: 4752 AN: 4810

European-Finnish (FIN) AF: 0.931 AC: 9838 AN: 10572

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.942 AC: 64051 AN: 68002

Other (OTH) AF: 0.948 AC: 2000 AN: 2110

Alfa AF: 0.934 Hom.: 15767

Bravo AF: 0.941

Asia WGS AF: 0.980 AC: 3408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.2
DANN	Benign	0.80
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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: rs7539166; hg19: chr1-15495905;