1-15177907-T-G

Variant names:

• chr1-15177907-T-G
• rs10927698
• NM_001136218.2:c.-267+23953T>G

Variant summary

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

The NM_001136218.2(TMEM51):​c.-267+23953T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 151,956 control chromosomes in the GnomAD database, including 11,649 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 0.36 (11649 hom., cov: 32)
• Consequence: TMEM51 NM_001136218.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96
• Publications: 8 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136218.2. 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+23953T>G		intron	N/A	NP_001129690.1
	TMEM51	NM_001136216.2		c.-267+25123T>G		intron	N/A	NP_001129688.1
	TMEM51	NM_001136217.2		c.-194+25123T>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+23953T>G		intron	N/A	ENSP00000365176.1
	TMEM51	ENST00000400796.7	TSL:1	c.-194+23953T>G		intron	N/A	ENSP00000383600.2
	TMEM51	ENST00000434578.6	TSL:1	c.-267+23953T>G		intron	N/A	ENSP00000409665.2

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55404 AN: 151838 Hom.: 11635 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.365 AC: 55430 AN: 151956 Hom.: 11649 Cov.: 32 AF XY: 0.370 AC XY: 27510 AN XY: 74260

African (AFR) AF: 0.151 AC: 6270 AN: 41460

American (AMR) AF: 0.498 AC: 7597 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1657 AN: 3470

East Asian (EAS) AF: 0.597 AC: 3077 AN: 5158

South Asian (SAS) AF: 0.429 AC: 2066 AN: 4820

European-Finnish (FIN) AF: 0.422 AC: 4453 AN: 10554

Middle Eastern (MID) AF: 0.459 AC: 133 AN: 290

European-Non Finnish (NFE) AF: 0.428 AC: 29053 AN: 67928

Other (OTH) AF: 0.398 AC: 839 AN: 2106

Alfa AF: 0.413 Hom.: 42481

Bravo AF: 0.365

Asia WGS AF: 0.496 AC: 1722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.14
DANN	Benign	0.57
PhyloP100		-2.0
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: rs10927698; hg19: chr1-15504403;