chr6-41787719-G-T

Position:

• chr6-41787719-G-T

Variant summary

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

The ENST00000398881.4(TOMM6):​c.22G>T​(p.Val8Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TOMM6 ENST00000398881.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40

Genes affected

TOMM6 (HGNC:34528): (translocase of outer mitochondrial membrane 6) Predicted to be involved in protein transport. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000124593 (HGNC:):

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=0.09975138).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOMM6	NM_001382294.1	c.22G>T	p.Val8Leu	missense_variant	1/3	ENST00000398881.4	NP_001369223.1
TOMM6	NM_001134493.2	c.22G>T	p.Val8Leu	missense_variant	1/3		NP_001127965.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOMM6	ENST00000398881.4	c.22G>T	p.Val8Leu	missense_variant	1/3	1	NM_001382294.1	ENSP00000381856.3
ENSG00000124593	ENST00000335515.10	n.*590G>T		non_coding_transcript_exon_variant	7/9	2		ENSP00000335185.6
ENSG00000124593	ENST00000335515.10	n.*590G>T		3_prime_UTR_variant	7/9	2		ENSP00000335185.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399410 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690208

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: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 05, 2023

The c.22G>T (p.V8L) alteration is located in exon 1 (coding exon 1) of the TOMM6 gene. This alteration results from a G to T substitution at nucleotide position 22, causing the valine (V) at amino acid position 8 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.057	T;T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.75	.;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.064
Sift	Uncertain	0.013	D;D
Sift4G	Benign	0.064	T;T
Polyphen		0.0010	B;B
Vest4		0.23
MutPred		0.13		Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);
MVP		0.030
ClinPred		0.50	T
GERP RS		3.4
Varity_R		0.21
gMVP		0.54

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: chr6-41755457;