chr12-51055962-G-A

Variant names:

• chr12-51055962-G-A
• NM_015416.5:c.601G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015416.5(LETMD1):​c.601G>A​(p.Val201Ile) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LETMD1 NM_015416.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41

Genes affected

LETMD1 (HGNC:24241): (LETM1 domain containing 1) This gene encodes a mitochondrial outer membrane protein. It has a potential role in tumorigenesis, which may result from negative regulation of the p53 tumor suppressor gene. Alternatively spliced transcript variants have been noted for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06040743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LETMD1	NM_015416.5	c.601G>A	p.Val201Ile	missense_variant	Exon 5 of 9	ENST00000262055.9	NP_056231.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LETMD1	ENST00000262055.9	c.601G>A	p.Val201Ile	missense_variant	Exon 5 of 9	1	NM_015416.5	ENSP00000262055.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Benign	0.94
DEOGEN2	Benign	0.0081	.;.;T;T;.;T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.088	N
LIST_S2	Benign	0.71	T;T;T;T;T;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.060	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	.;.;L;.;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.60	N;N;N;N;N;N
REVEL	Benign	0.055
Sift	Benign	0.30	T;T;T;T;T;T
Sift4G	Benign	0.34	T;T;T;T;T;T
Polyphen		0.10, 0.0010, 0.066	.;.;B;B;.;B
Vest4		0.11, 0.12, 0.16, 0.10
MutPred		0.51		.;.;Gain of catalytic residue at P203 (P = 0.0012);.;.;.;
MVP		0.19
MPC		0.23
ClinPred		0.037	T
GERP RS		2.2
Varity_R		0.016
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr12-51449745;