rs72874051

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-15215414-C-A
• chr1-15215414-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001136218.2(TMEM51):​c.327C>A​(p.His109Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H109H) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TMEM51 NM_001136218.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040894717).

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>A	p.His109Gln	missense	Exon 3 of 4	NP_001129690.1	Q9NW97
	TMEM51	NM_001136216.2		c.327C>A	p.His109Gln	missense	Exon 3 of 4	NP_001129688.1	Q9NW97
	TMEM51	NM_001136217.2		c.327C>A	p.His109Gln	missense	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>A	p.His109Gln	missense	Exon 3 of 4	ENSP00000365176.1	Q9NW97
	TMEM51	ENST00000400796.7	TSL:1	c.327C>A	p.His109Gln	missense	Exon 2 of 3	ENSP00000383600.2	Q9NW97
	TMEM51	ENST00000434578.6	TSL:1	c.327C>A	p.His109Gln	missense	Exon 3 of 4	ENSP00000409665.2	Q9BSA0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451294 Hom.: 0 Cov.: 33 AF XY: 0.00000139 AC XY: 1 AN XY: 721146

African (AFR) AF: 0.00 AC: 0 AN: 33360

American (AMR) AF: 0.00 AC: 0 AN: 44530

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25954

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

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85868

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5002

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108446

Other (OTH) AF: 0.00 AC: 0 AN: 60040

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.0020
DANN	Benign	0.47
DEOGEN2	Benign	0.020	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-2.3
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.044
Sift	Benign	0.36	T
Sift4G	Benign	0.35	T
Polyphen		0.0	B
Vest4		0.081
MutPred		0.072		Gain of relative solvent accessibility (P = 0.1066)
MVP		0.093
MPC		0.18
ClinPred		0.13	T
GERP RS		-11
Varity_R		0.037
gMVP		0.14
Mutation Taster		=98/2	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: rs72874051; hg19: chr1-15541910; COSMIC: COSV65690881;