rs11550233

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001636.4(SLC25A6):​c.225T>G​(p.Leu75Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,614,122 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 83 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00070 ( 0 hom., 45 hem., cov: 32)
Exomes 𝑓: 0.000072 ( 0 hom. 38 hem. )

Consequence

SLC25A6
NM_001636.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0300
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 -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
Variant X-1389614-A-C is Benign according to our data. Variant chrX-1389614-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 709133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.03 with no splicing effect.
BS2
High Hemizygotes in GnomAd4 at 45 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC25A6NM_001636.4 linkc.225T>G p.Leu75Leu 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.225T>G p.Leu75Leu synonymous_variant Exon 2 of 4 1 NM_001636.4 ENSP00000370808.5 P12236
SLC25A6ENST00000475167.6 linkn.418T>G non_coding_transcript_exon_variant Exon 3 of 4 2
SLC25A6ENST00000484026.6 linkn.406T>G non_coding_transcript_exon_variant Exon 3 of 4 5

Frequencies

GnomAD3 genomes
AF:
0.000697
AC:
106
AN:
152122
Hom.:
0
Cov.:
32
AF XY:
0.000592
AC XY:
44
AN XY:
74308
show subpopulations
Gnomad AFR
AF:
0.00249
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000223
AC:
56
AN:
251490
Hom.:
0
AF XY:
0.000125
AC XY:
17
AN XY:
135920
show subpopulations
Gnomad AFR exome
AF:
0.00295
Gnomad AMR exome
AF:
0.000202
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:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000718
AC:
105
AN:
1461882
Hom.:
0
Cov.:
38
AF XY:
0.0000523
AC XY:
38
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00215
Gnomad4 AMR exome
AF:
0.000246
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:
0.00000270
Gnomad4 OTH exome
AF:
0.000281
GnomAD4 genome
AF:
0.000696
AC:
106
AN:
152240
Hom.:
0
Cov.:
32
AF XY:
0.000605
AC XY:
45
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.00248
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000473
Bravo
AF:
0.000740

ClinVar

Significance: Likely 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: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely 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
-0.73
CADD
Benign
10
DANN
Benign
0.51
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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: rs11550233; hg19: chrX-1508507; API