6-41787723-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001382294.1(TOMM6):​c.26G>A​(p.Ser9Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000253 in 1,551,598 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

TOMM6
NM_001382294.1 missense

Scores

1
17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.27
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.043442756).
BP6
Variant 6-41787723-G-A is Benign according to our data. Variant chr6-41787723-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2458684.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TOMM6NM_001382294.1 linkuse as main transcriptc.26G>A p.Ser9Asn missense_variant 1/3 ENST00000398881.4 NP_001369223.1
TOMM6NM_001134493.2 linkuse as main transcriptc.26G>A p.Ser9Asn missense_variant 1/3 NP_001127965.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TOMM6ENST00000398881.4 linkuse as main transcriptc.26G>A p.Ser9Asn missense_variant 1/31 NM_001382294.1 ENSP00000381856 P1
TOMM6ENST00000398884.7 linkuse as main transcriptc.26G>A p.Ser9Asn missense_variant 1/31 ENSP00000381859 P1

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
152192
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000895
AC:
14
AN:
156478
Hom.:
0
AF XY:
0.0000964
AC XY:
8
AN XY:
82954
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000231
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000269
AC:
376
AN:
1399406
Hom.:
0
Cov.:
31
AF XY:
0.000238
AC XY:
164
AN XY:
690208
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000280
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:
0.000342
Gnomad4 OTH exome
AF:
0.000103
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
152192
Hom.:
0
Cov.:
33
AF XY:
0.0000538
AC XY:
4
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000158
Hom.:
0
Bravo
AF:
0.000162
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000519
AC:
2
ExAC
AF:
0.0000403
AC:
1

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsJan 26, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.088
BayesDel_addAF
Benign
-0.61
T
BayesDel_noAF
Benign
-0.83
CADD
Benign
0.0030
DANN
Benign
0.85
DEOGEN2
Benign
0.061
T;T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.012
N
LIST_S2
Benign
0.35
.;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.043
T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-1.3
N;N
REVEL
Benign
0.013
Sift
Benign
0.23
T;T
Sift4G
Uncertain
0.014
D;D
Polyphen
0.0
B;B
Vest4
0.079
MVP
0.014
ClinPred
0.032
T
GERP RS
-3.5
RBP_binding_hub_radar
1.0
RBP_regulation_power_radar
2.1
Varity_R
0.084
gMVP
0.36

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.

Other links and lift over

dbSNP: rs574630326; hg19: chr6-41755461; API