rs755273479

Variant names:

• chr1-15219457-C-A
• rs755273479
• NM_001136218.2:c.476C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-15219457-C-A
• chr1-15219457-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001136218.2(TMEM51):​c.476C>A​(p.Pro159Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. P159L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM51 NM_001136218.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.81
• 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.829

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.476C>A	p.Pro159Gln	missense	Exon 4 of 4	NP_001129690.1	Q9NW97
	TMEM51	NM_001136216.2		c.476C>A	p.Pro159Gln	missense	Exon 4 of 4	NP_001129688.1	Q9NW97
	TMEM51	NM_001136217.2		c.476C>A	p.Pro159Gln	missense	Exon 3 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.476C>A	p.Pro159Gln	missense	Exon 4 of 4	ENSP00000365176.1	Q9NW97
	TMEM51	ENST00000400796.7	TSL:1	c.476C>A	p.Pro159Gln	missense	Exon 3 of 3	ENSP00000383600.2	Q9NW97
	TMEM51	ENST00000434578.6	TSL:1	c.*64C>A		3_prime_UTR	Exon 4 of 4	ENSP00000409665.2	Q9BSA0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.082	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Benign	-0.48	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		6.8
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.82
MutPred		0.30		Gain of solvent accessibility (P = 0.0202)
MVP		0.41
MPC		0.70
ClinPred		1.0	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.80
gMVP		0.70
Mutation Taster		=28/72	disease causing

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: rs755273479; hg19: chr1-15545953;