chr8-38392806-C-A

Variant names:

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

Variant summary

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

The NM_001286819.2(LETM2):​c.312C>A​(p.Ser104Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LETM2 NM_001286819.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.430

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

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=0.1109615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LETM2	NM_001286819.2	c.312C>A	p.Ser104Arg	missense_variant	Exon 3 of 11	ENST00000379957.9	NP_001273748.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LETM2	ENST00000379957.9	c.312C>A	p.Ser104Arg	missense_variant	Exon 3 of 11	5	NM_001286819.2	ENSP00000369291.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461842 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727210

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.022	.;T;.;T;T;.;T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.80	T;T;T;T;T;T;T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.11	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	.;.;.;.;L;.;.
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.0	D;N;N;N;N;N;D
REVEL	Benign	0.037
Sift	Uncertain	0.019	D;D;D;D;T;D;D
Sift4G	Uncertain	0.012	D;T;T;T;T;T;D
Polyphen		0.98, 0.20, 0.68	.;D;.;B;P;.;.
Vest4		0.064, 0.12, 0.12, 0.098, 0.10
MutPred		0.20		Loss of glycosylation at S104 (P = 0.0259);Loss of glycosylation at S104 (P = 0.0259);.;Loss of glycosylation at S104 (P = 0.0259);Loss of glycosylation at S104 (P = 0.0259);.;Loss of glycosylation at S104 (P = 0.0259);
MVP		0.048
MPC		0.063
ClinPred		0.45	T
GERP RS		1.8
Varity_R		0.069
gMVP		0.30

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: chr8-38250324;