8-38392690-G-A

Variant names:

• chr8-38392690-G-A
• NM_001286819.2:c.196G>A

Variant summary

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

The NM_001286819.2(LETM2):​c.196G>A​(p.Val66Ile) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LETM2 NM_001286819.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0260
• Publications: 0 publications found

Genes affected

LETM2 (HGNC:14648): (leucine zipper and EF-hand containing transmembrane protein 2) Predicted to enable ribosome binding activity. Predicted to be involved in cellular metal ion homeostasis. Predicted to be located in mitochondrial inner membrane. 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=0.060481757).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286819.2. 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
	LETM2	NM_001286819.2	MANE Select	c.196G>A	p.Val66Ile	missense	Exon 3 of 11	NP_001273748.1	Q2VYF4-1
	LETM2	NM_001199659.3		c.55G>A	p.Val19Ile	missense	Exon 3 of 11	NP_001186588.1	Q2VYF4-2
	LETM2	NM_001330515.2		c.196G>A	p.Val66Ile	missense	Exon 3 of 10	NP_001317444.1	E9PMA4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LETM2	ENST00000379957.9	TSL:5 MANE Select	c.196G>A	p.Val66Ile	missense	Exon 3 of 11	ENSP00000369291.4	Q2VYF4-1
	LETM2	ENST00000523983.6	TSL:1	c.55G>A	p.Val19Ile	missense	Exon 3 of 11	ENSP00000428765.2	Q2VYF4-2
	LETM2	ENST00000519476.6	TSL:1	c.196G>A	p.Val66Ile	missense	Exon 3 of 3	ENSP00000429269.2	A8K1M9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.28
DANN	Benign	0.36
DEOGEN2	Benign	0.0099	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N
PhyloP100		0.026
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.0090
Sift	Benign	0.23	T
Sift4G	Benign	0.32	T
Polyphen		0.0010	B
Vest4		0.023
MutPred		0.24		Loss of sheet (P = 0.0315)
MVP		0.014
MPC		0.049
ClinPred		0.079	T
GERP RS		0.41
Varity_R		0.034
gMVP		0.058
Mutation Taster		=96/4	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

hg19: chr8-38250208;