rs1143655

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001636.4(SLC25A6):​c.267C>T​(p.Phe89Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00278 in 1,614,166 control chromosomes in the GnomAD database, including 131 homozygotes. There are 1,949 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 78 hom., 1030 hem., cov: 32)
Exomes 𝑓: 0.0015 ( 53 hom. 919 hem. )

Consequence

SLC25A6
NM_001636.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.393
Variant links:
Genes affected
SLC25A6 (HGNC:10992): (solute carrier family 25 member 6) This gene is a member of the mitochondrial carrier subfamily of solute carrier protein genes. The product of this gene functions as a gated pore that translocates ADP from the cytoplasm into the mitochondrial matrix and ATP from the mitochondrial matrix into the cytoplasm. The protein is implicated in the function of the permability transition pore complex (PTPC), which regulates the release of mitochondrial products that induce apoptosis. The human genome contains several non-transcribed pseudogenes of this gene. [provided by RefSeq, Jun 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
Variant X-1389572-G-A is Benign according to our data. Variant chrX-1389572-G-A is described in ClinVar as [Benign]. Clinvar id is 785691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.393 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0503 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC25A6NM_001636.4 linkc.267C>T p.Phe89Phe synonymous_variant Exon 2 of 4 ENST00000381401.11 NP_001627.2 P12236Q6I9V5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC25A6ENST00000381401.11 linkc.267C>T p.Phe89Phe synonymous_variant Exon 2 of 4 1 NM_001636.4 ENSP00000370808.5 P12236
SLC25A6ENST00000475167.6 linkn.460C>T non_coding_transcript_exon_variant Exon 3 of 4 2
SLC25A6ENST00000484026.6 linkn.448C>T non_coding_transcript_exon_variant Exon 3 of 4 5

Frequencies

GnomAD3 genomes
AF:
0.0148
AC:
2252
AN:
152170
Hom.:
77
Cov.:
32
AF XY:
0.0138
AC XY:
1024
AN XY:
74348
show subpopulations
Gnomad AFR
AF:
0.0520
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00419
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000620
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.00909
GnomAD3 exomes
AF:
0.00377
AC:
949
AN:
251492
Hom.:
29
AF XY:
0.00260
AC XY:
353
AN XY:
135922
show subpopulations
Gnomad AFR exome
AF:
0.0528
Gnomad AMR exome
AF:
0.00191
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000105
Gnomad OTH exome
AF:
0.000977
GnomAD4 exome
AF:
0.00152
AC:
2222
AN:
1461878
Hom.:
53
Cov.:
38
AF XY:
0.00126
AC XY:
919
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.0550
Gnomad4 AMR exome
AF:
0.00197
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000927
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000612
Gnomad4 OTH exome
AF:
0.00333
GnomAD4 genome
AF:
0.0149
AC:
2263
AN:
152288
Hom.:
78
Cov.:
32
AF XY:
0.0138
AC XY:
1030
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.0521
Gnomad4 AMR
AF:
0.00419
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.00900
Bravo
AF:
0.0172
EpiCase
AF:
0.000109
EpiControl
AF:
0.000237

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.38
CADD
Benign
11
DANN
Benign
0.76

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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: rs1143655; hg19: chrX-1508465; API