NM_001636.4:c.429G>A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001636.4(SLC25A6):​c.429G>A​(p.Ala143Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0034 in 1,613,714 control chromosomes in the GnomAD database, including 14 homozygotes. There are 2,624 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 0.0023 ( 0 hom., 171 hem., cov: 32)
Exomes 𝑓: 0.0035 ( 14 hom. 2453 hem. )

Consequence

SLC25A6
NM_001636.4 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.191
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 -15 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
Variant X-1389410-C-T is Benign according to our data. Variant chrX-1389410-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 788322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.191 with no splicing effect.
BS2
High Hemizygotes in GnomAd4 at 171 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC25A6NM_001636.4 linkc.429G>A p.Ala143Ala 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.429G>A p.Ala143Ala synonymous_variant Exon 2 of 4 1 NM_001636.4 ENSP00000370808.5 P12236
SLC25A6ENST00000475167.6 linkn.622G>A non_coding_transcript_exon_variant Exon 3 of 4 2
SLC25A6ENST00000484026.6 linkn.610G>A non_coding_transcript_exon_variant Exon 3 of 4 5

Frequencies

GnomAD3 genomes
AF:
0.00231
AC:
351
AN:
152200
Hom.:
0
Cov.:
32
AF XY:
0.00230
AC XY:
171
AN XY:
74340
show subpopulations
Gnomad AFR
AF:
0.000506
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00465
Gnomad ASJ
AF:
0.00375
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000565
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00345
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00190
AC:
476
AN:
251174
Hom.:
2
AF XY:
0.00194
AC XY:
263
AN XY:
135754
show subpopulations
Gnomad AFR exome
AF:
0.000431
Gnomad AMR exome
AF:
0.00231
Gnomad ASJ exome
AF:
0.00327
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.000139
Gnomad NFE exome
AF:
0.00302
Gnomad OTH exome
AF:
0.00131
GnomAD4 exome
AF:
0.00352
AC:
5137
AN:
1461396
Hom.:
14
Cov.:
33
AF XY:
0.00337
AC XY:
2453
AN XY:
726984
show subpopulations
Gnomad4 AFR exome
AF:
0.000359
Gnomad4 AMR exome
AF:
0.00219
Gnomad4 ASJ exome
AF:
0.00321
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.000543
Gnomad4 NFE exome
AF:
0.00425
Gnomad4 OTH exome
AF:
0.00300
GnomAD4 genome
AF:
0.00230
AC:
351
AN:
152318
Hom.:
0
Cov.:
32
AF XY:
0.00230
AC XY:
171
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.000505
Gnomad4 AMR
AF:
0.00464
Gnomad4 ASJ
AF:
0.00375
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000565
Gnomad4 NFE
AF:
0.00345
Gnomad4 OTH
AF:
0.00237
Bravo
AF:
0.00218
EpiCase
AF:
0.00409
EpiControl
AF:
0.00267

ClinVar

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

Submissions by phenotype

not provided Benign:2
Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.46
CADD
Benign
1.6
DANN
Benign
0.71
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.4

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: rs143216483; hg19: chrX-1508303; COSMIC: COSV67317980; API