1-15219627-T-G

Variant names:

• chr1-15219627-T-G
• NM_001136218.2:c.646T>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136218.2(TMEM51):​c.646T>G​(p.Phe216Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM51 NM_001136218.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.35

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21928385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM51	NM_001136218.2	c.646T>G	p.Phe216Val	missense_variant	Exon 4 of 4	ENST00000376008.3	NP_001129690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM51	ENST00000376008.3	c.646T>G	p.Phe216Val	missense_variant	Exon 4 of 4	2	NM_001136218.2	ENSP00000365176.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.646T>G (p.F216V) alteration is located in exon 4 (coding exon 2) of the TMEM51 gene. This alteration results from a T to G substitution at nucleotide position 646, causing the phenylalanine (F) at amino acid position 216 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.071	T;T;T;T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.70	T;.;.;.
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.6	M;M;M;M
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.1	N;N;N;N
REVEL	Benign	0.090
Sift	Benign	0.066	T;T;T;T
Sift4G	Benign	0.20	T;T;T;T
Polyphen		0.66	P;P;P;P
Vest4		0.34
MutPred		0.22		Gain of MoRF binding (P = 0.0796);Gain of MoRF binding (P = 0.0796);Gain of MoRF binding (P = 0.0796);Gain of MoRF binding (P = 0.0796);
MVP		0.082
MPC		0.38
ClinPred		0.89	D
GERP RS		5.5
Varity_R		0.097
gMVP		0.19

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-15546123;