NM_001286819.2:c.312C>T

Variant names:

• chr8-38392806-C-T
• rs369522263
• NM_001286819.2:c.312C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001286819.2(LETM2):​c.312C>T​(p.Ser104Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LETM2 NM_001286819.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.430
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=0.43 with no splicing effect.

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.312C>T	p.Ser104Ser	synonymous	Exon 3 of 11	NP_001273748.1	Q2VYF4-1
	LETM2	NM_001199659.3		c.171C>T	p.Ser57Ser	synonymous	Exon 3 of 11	NP_001186588.1	Q2VYF4-2
	LETM2	NM_001330515.2		c.312C>T	p.Ser104Ser	synonymous	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.312C>T	p.Ser104Ser	synonymous	Exon 3 of 11	ENSP00000369291.4	Q2VYF4-1
	LETM2	ENST00000523983.6	TSL:1	c.171C>T	p.Ser57Ser	synonymous	Exon 3 of 11	ENSP00000428765.2	Q2VYF4-2
	LETM2	ENST00000519476.6	TSL:1	c.312C>T	p.Ser104Ser	synonymous	Exon 3 of 3	ENSP00000429269.2	A8K1M9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461842 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727210

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.1
DANN	Benign	0.53
PhyloP100		0.43

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: rs369522263; hg19: chr8-38250324;