dbSNP rs372713133: TOMM20L:p.Asn30His (chr14-58396045-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_207377.3(TOMM20L):c.88A>C(p.Asn30His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000942 in 1,273,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)

Exomes 𝑓: 0.0000094 ( 0 hom. )

Consequence

TOMM20L
NM_207377.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.969

Variant links:

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]

TOMM20L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.14575946).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM20L	NM_207377.3 link	c.88A>C	p.Asn30His	missense_variant	Exon 1 of 5	ENST00000360945.7	NP_997260.1	Q6UXN7
TOMM20L	XM_011536742.4 link	c.88A>C	p.Asn30His	missense_variant	Exon 1 of 5		XP_011535044.1
TOMM20L	XM_011536743.3 link	c.88A>C	p.Asn30His	missense_variant	Exon 1 of 5		XP_011535045.1
TOMM20L	XM_011536744.4 link	c.88A>C	p.Asn30His	missense_variant	Exon 1 of 3		XP_011535046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOMM20L	ENST00000360945.7 link	c.88A>C	p.Asn30His	missense_variant	Exon 1 of 5	1	NM_207377.3	ENSP00000354204.2		Q6UXN7
TOMM20L	ENST00000557754.1 link	n.88A>C		non_coding_transcript_exon_variant	Exon 1 of 4	1		ENSP00000451683.1		G3V4A4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000133

AC:

AN:

150826

Hom.:

AF XY:

0.0000229

AC XY:

AN XY:

87198

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000263

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000942

AC:

AN:

1273552

Hom.:

Cov.:

AF XY:

0.0000127

AC XY:

AN XY:

627862

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000397

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000173

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.055

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.48

M_CAP

Benign

0.014

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.5

REVEL

Benign

0.065

Sift

Benign

0.035

Sift4G

Uncertain

0.0090

Polyphen

0.074

Vest4

0.26

MutPred

0.73

Loss of MoRF binding (P = 0.112);

MVP

0.014

MPC

0.58

ClinPred

0.073

GERP RS

2.0

Varity_R

0.15

gMVP

0.24

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over