1-15215414-C-T

Variant names:

• chr1-15215414-C-T
• rs72874051
• NM_001136218.2:c.327C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001136218.2(TMEM51):​c.327C>T​(p.His109His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000809 in 1,603,672 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00048 (4 hom.)
• Consequence: TMEM51 NM_001136218.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.28
• Publications: 1 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-15215414-C-T is Benign according to our data. Variant chr1-15215414-C-T is described in ClinVar as Benign. ClinVar VariationId is 716269.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.28 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM51	NM_001136218.2	MANE Select	c.327C>T	p.His109His	synonymous	Exon 3 of 4	NP_001129690.1	Q9NW97
	TMEM51	NM_001136216.2		c.327C>T	p.His109His	synonymous	Exon 3 of 4	NP_001129688.1	Q9NW97
	TMEM51	NM_001136217.2		c.327C>T	p.His109His	synonymous	Exon 2 of 3	NP_001129689.1	Q9NW97

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM51	ENST00000376008.3	TSL:2 MANE Select	c.327C>T	p.His109His	synonymous	Exon 3 of 4	ENSP00000365176.1	Q9NW97
	TMEM51	ENST00000400796.7	TSL:1	c.327C>T	p.His109His	synonymous	Exon 2 of 3	ENSP00000383600.2	Q9NW97
	TMEM51	ENST00000434578.6	TSL:1	c.327C>T	p.His109His	synonymous	Exon 3 of 4	ENSP00000409665.2	Q9BSA0

Frequencies

GnomAD3 genomes AF: 0.00389 AC: 593 AN: 152260 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00654

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00716

GnomAD2 exomes AF: 0.00116 AC: 280 AN: 241652 AF XY: 0.000746

Gnomad AFR exome AF: 0.0112

Gnomad AMR exome AF: 0.00152

Gnomad ASJ exome AF: 0.00276

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000137

Gnomad OTH exome AF: 0.00134

GnomAD4 exome AF: 0.000484 AC: 702 AN: 1451294 Hom.: 4 Cov.: 33 AF XY: 0.000410 AC XY: 296 AN XY: 721146

African (AFR) AF: 0.0120 AC: 400 AN: 33360

American (AMR) AF: 0.00202 AC: 90 AN: 44530

Ashkenazi Jewish (ASJ) AF: 0.00208 AC: 54 AN: 25954

East Asian (EAS) AF: 0.00 AC: 0 AN: 39578

South Asian (SAS) AF: 0.0000932 AC: 8 AN: 85868

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48516

Middle Eastern (MID) AF: 0.00220 AC: 11 AN: 5002

European-Non Finnish (NFE) AF: 0.0000577 AC: 64 AN: 1108446

Other (OTH) AF: 0.00125 AC: 75 AN: 60040

GnomAD4 genome AF: 0.00391 AC: 596 AN: 152378 Hom.: 4 Cov.: 33 AF XY: 0.00399 AC XY: 297 AN XY: 74512

African (AFR) AF: 0.0112 AC: 466 AN: 41600

American (AMR) AF: 0.00653 AC: 100 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68038

Other (OTH) AF: 0.00709 AC: 15 AN: 2116

Alfa AF: 0.00231 Hom.: 0

Bravo AF: 0.00512

Asia WGS AF: 0.00173 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.14
DANN	Benign	0.46
PhyloP100		-2.3
Mutation Taster		=100/0	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: rs72874051; hg19: chr1-15541910; COSMIC: COSV105315046;