rs1566740501

Variant names:

• chr14-58396061-G-A
• rs1566740501
• NM_207377.3:c.104G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-58396061-G-A
• chr14-58396061-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207377.3(TOMM20L):​c.104G>A​(p.Gly35Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000794 in 1,260,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: TOMM20L NM_207377.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.33
• Publications: 0 publications found

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-DT (HGNC:55443): (TOMM20L divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23093605).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207377.3. 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
	TOMM20L	NM_207377.3	MANE Select	c.104G>A	p.Gly35Glu	missense	Exon 1 of 5	NP_997260.1	Q6UXN7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOMM20L	ENST00000360945.7	TSL:1 MANE Select	c.104G>A	p.Gly35Glu	missense	Exon 1 of 5	ENSP00000354204.2	Q6UXN7
	TOMM20L	ENST00000557754.1	TSL:1	n.104G>A		non_coding_transcript_exon	Exon 1 of 4	ENSP00000451683.1	G3V4A4
	TOMM20L-DT	ENST00000556390.2	TSL:3	n.-235C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000704 AC: 1 AN: 141970 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000699

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 7.94e-7 AC: 1 AN: 1260158 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 620080

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25630

American (AMR) AF: 0.0000440 AC: 1 AN: 22710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19500

East Asian (EAS) AF: 0.00 AC: 0 AN: 30072

South Asian (SAS) AF: 0.00 AC: 0 AN: 51374

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4850

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1010784

Other (OTH) AF: 0.00 AC: 0 AN: 50038

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.13
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.67	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		2.3
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.046
Sift	Benign	0.032	D
Sift4G	Benign	0.26	T
Polyphen		0.78	P
Vest4		0.36
MutPred		0.40		Gain of solvent accessibility (P = 0.024)
MVP		0.21
MPC		1.2
ClinPred		0.76	D
GERP RS		2.8
PromoterAI		0.032	Neutral
Varity_R		0.55
gMVP		0.047
Mutation Taster		=93/7	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

dbSNP: rs1566740501; hg19: chr14-58862779;