rs7205

Variant names:

• chrX-1389431-G-A
• rs7205
• NM_001636.4:c.408C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_001636.4(SLC25A6):​c.408C>T​(p.Phe136Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,613,326 control chromosomes in the GnomAD database, including 61,161 homozygotes. There are 216,469 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Synonymous variant affecting the same amino acid position (i.e. F136F) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.31 (8165 hom., 22833 hem., cov: 32)
  • Exomes 𝑓: 0.26 (52996 hom. 193636 hem.)
• Consequence: SLC25A6 NM_001636.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.09

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant X-1389431-G-A is Benign according to our data. Variant chrX-1389431-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3036125.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A6	NM_001636.4	c.408C>T	p.Phe136Phe	synonymous_variant	Exon 2 of 4	ENST00000381401.11	NP_001627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A6	ENST00000381401.11	c.408C>T	p.Phe136Phe	synonymous_variant	Exon 2 of 4	1	NM_001636.4	ENSP00000370808.5
SLC25A6	ENST00000475167.6	n.601C>T		non_coding_transcript_exon_variant	Exon 3 of 4	2
SLC25A6	ENST00000484026.6	n.589C>T		non_coding_transcript_exon_variant	Exon 3 of 4	5

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47061 AN: 151972 Hom.: 8151 Cov.: 32

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.302

GnomAD2 exomes AF: 0.283 AC: 71050 AN: 251204 AF XY: 0.286

Gnomad AFR exome AF: 0.459

Gnomad AMR exome AF: 0.323

Gnomad ASJ exome AF: 0.314

Gnomad EAS exome AF: 0.0888

Gnomad FIN exome AF: 0.232

Gnomad NFE exome AF: 0.255

Gnomad OTH exome AF: 0.280

GnomAD4 exome AF: 0.263 AC: 384692 AN: 1461234 Hom.: 52996 Cov.: 70 AF XY: 0.266 AC XY: 193636 AN XY: 726808

Gnomad4 AFR exome AF: 0.454 AC: 15187 AN: 33462

Gnomad4 AMR exome AF: 0.324 AC: 14481 AN: 44710

Gnomad4 ASJ exome AF: 0.311 AC: 8120 AN: 26126

Gnomad4 EAS exome AF: 0.124 AC: 4915 AN: 39694

Gnomad4 SAS exome AF: 0.389 AC: 33512 AN: 86244

Gnomad4 FIN exome AF: 0.232 AC: 12363 AN: 53382

Gnomad4 NFE exome AF: 0.250 AC: 277796 AN: 1111654

Gnomad4 Remaining exome AF: 0.277 AC: 16704 AN: 60348

GnomAD4 genome AF: 0.310 AC: 47099 AN: 152092 Hom.: 8165 Cov.: 32 AF XY: 0.307 AC XY: 22833 AN XY: 74334

Gnomad4 AFR AF: 0.448 AC: 0.447736 AN: 0.447736

Gnomad4 AMR AF: 0.298 AC: 0.297775 AN: 0.297775

Gnomad4 ASJ AF: 0.300 AC: 0.299712 AN: 0.299712

Gnomad4 EAS AF: 0.105 AC: 0.105019 AN: 0.105019

Gnomad4 SAS AF: 0.374 AC: 0.374014 AN: 0.374014

Gnomad4 FIN AF: 0.227 AC: 0.226663 AN: 0.226663

Gnomad4 NFE AF: 0.254 AC: 0.25384 AN: 0.25384

Gnomad4 OTH AF: 0.300 AC: 0.300378 AN: 0.300378

Bravo AF: 0.320

EpiCase AF: 0.264

EpiControl AF: 0.257

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SLC25A6-related disorder Benign:1

Feb 16, 2021

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	7.5
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs7205; hg19: chrX-1508324; COSMIC: COSV67317506;