chrX-1389431-G-A

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).

• 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
• Publications: 0 publications found

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001636.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A6	NM_001636.4	MANE Select	c.408C>T	p.Phe136Phe	synonymous	Exon 2 of 4	NP_001627.2	P12236

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A6	ENST00000381401.11	TSL:1 MANE Select	c.408C>T	p.Phe136Phe	synonymous	Exon 2 of 4	ENSP00000370808.5	P12236
	SLC25A6	ENST00000871943.1		c.408C>T	p.Phe136Phe	synonymous	Exon 2 of 4	ENSP00000542002.1
	SLC25A6	ENST00000871942.1		c.408C>T	p.Phe136Phe	synonymous	Exon 3 of 5	ENSP00000542001.1

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

African (AFR) AF: 0.454 AC: 15187 AN: 33462

American (AMR) AF: 0.324 AC: 14481 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 8120 AN: 26126

East Asian (EAS) AF: 0.124 AC: 4915 AN: 39694

South Asian (SAS) AF: 0.389 AC: 33512 AN: 86244

European-Finnish (FIN) AF: 0.232 AC: 12363 AN: 53382

Middle Eastern (MID) AF: 0.287 AC: 1614 AN: 5614

European-Non Finnish (NFE) AF: 0.250 AC: 277796 AN: 1111654

Other (OTH) 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

African (AFR) AF: 0.448 AC: 18573 AN: 41482

American (AMR) AF: 0.298 AC: 4550 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1040 AN: 3470

East Asian (EAS) AF: 0.105 AC: 544 AN: 5180

South Asian (SAS) AF: 0.374 AC: 1802 AN: 4818

European-Finnish (FIN) AF: 0.227 AC: 2399 AN: 10584

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17251 AN: 67960

Other (OTH) AF: 0.300 AC: 635 AN: 2114

Bravo AF: 0.320

EpiCase AF: 0.264

EpiControl AF: 0.257

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SLC25A6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	7.5
DANN	Benign	0.75
PhyloP100		1.1

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

Other links and lift over

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