rs2036075515

Variant names:

• chr14-58407343-A-G
• NM_207377.3:c.280A>G

Your query was ambiguous. Multiple possible variants found:

• chr14-58407343-A-G
• chr14-58407343-A-T

Variant summary

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

The NM_207377.3(TOMM20L):​c.280A>G​(p.Ile94Val) 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: 33)
• Consequence: TOMM20L NM_207377.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.409

Genes affected

TOMM20L (HGNC:33752): (translocase of outer mitochondrial membrane 20 like) Predicted to enable mitochondrion targeting sequence binding activity. Predicted to contribute to protein transmembrane transporter activity. Predicted to be involved in protein import into mitochondrial matrix and tRNA import into mitochondrion. Predicted to be integral component of membrane. Predicted to be part of mitochondrial outer membrane translocase complex. Predicted to be integral component of mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000258378 (HGNC:):

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=0.040943474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM20L	NM_207377.3	c.280A>G	p.Ile94Val	missense_variant	Exon 4 of 5	ENST00000360945.7	NP_997260.1
TOMM20L	XM_011536742.4	c.304A>G	p.Ile102Val	missense_variant	Exon 4 of 5		XP_011535044.1
TOMM20L	XM_011536743.3	c.304A>G	p.Ile102Val	missense_variant	Exon 4 of 5		XP_011535045.1
TOMM20L	XM_011536744.4	c.154A>G	p.Ile52Val	missense_variant	Exon 2 of 3		XP_011535046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOMM20L	ENST00000360945.7	c.280A>G	p.Ile94Val	missense_variant	Exon 4 of 5	1	NM_207377.3	ENSP00000354204.2
TOMM20L	ENST00000557754.1	n.198A>G		non_coding_transcript_exon_variant	Exon 3 of 4	1		ENSP00000451683.1
ENSG00000258378	ENST00000556734.1	n.374+8413A>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.6
DANN	Benign	0.42
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0058	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-2.2	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.62	N
REVEL	Benign	0.029
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.62		Gain of MoRF binding (P = 0.1003);
MVP		0.014
MPC		0.42
ClinPred		0.090	T
GERP RS		1.9
Varity_R		0.076
gMVP		0.071

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: chr14-58874061;