chrX-1387425-C-G

Variant names:

• chrX-1387425-C-G
• rs6644951
• NM_001636.4:c.599-6G>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001636.4(SLC25A6):​c.599-6G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 1,611,068 control chromosomes in the GnomAD database, including 271,161 homozygotes. There are 463,856 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.63 (30755 hom., 46852 hem., cov: 33)
  • Exomes 𝑓: 0.57 (240406 hom. 417004 hem.)
• Consequence: SLC25A6 NM_001636.4 splice_region, intron
• Scores: Splicing: ADA: 0.00002056
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.498
• 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant X-1387425-C-G is Benign according to our data. Variant chrX-1387425-C-G is described in ClinVar as Benign. ClinVar VariationId is 3036192.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.736 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.599-6G>C		splice_region intron	N/A	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.599-6G>C		splice_region intron	N/A	ENSP00000370808.5	P12236
	SLC25A6	ENST00000871943.1		c.677-6G>C		splice_region intron	N/A	ENSP00000542002.1
	SLC25A6	ENST00000871942.1		c.599-6G>C		splice_region intron	N/A	ENSP00000542001.1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95559 AN: 151936 Hom.: 30708 Cov.: 33

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.633

GnomAD2 exomes AF: 0.610 AC: 151528 AN: 248222 AF XY: 0.612

Gnomad AFR exome AF: 0.750

Gnomad AMR exome AF: 0.672

Gnomad ASJ exome AF: 0.701

Gnomad EAS exome AF: 0.471

Gnomad FIN exome AF: 0.592

Gnomad NFE exome AF: 0.562

Gnomad OTH exome AF: 0.618

GnomAD4 exome AF: 0.571 AC: 832513 AN: 1459014 Hom.: 240406 Cov.: 74 AF XY: 0.575 AC XY: 417004 AN XY: 725686

African (AFR) AF: 0.753 AC: 25187 AN: 33446

American (AMR) AF: 0.674 AC: 30086 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.696 AC: 18158 AN: 26078

East Asian (EAS) AF: 0.449 AC: 17819 AN: 39670

South Asian (SAS) AF: 0.712 AC: 61311 AN: 86170

European-Finnish (FIN) AF: 0.582 AC: 30325 AN: 52066

Middle Eastern (MID) AF: 0.642 AC: 3452 AN: 5376

European-Non Finnish (NFE) AF: 0.550 AC: 610739 AN: 1111244

Other (OTH) AF: 0.588 AC: 35436 AN: 60294

GnomAD4 genome AF: 0.629 AC: 95660 AN: 152054 Hom.: 30755 Cov.: 33 AF XY: 0.631 AC XY: 46852 AN XY: 74288

African (AFR) AF: 0.743 AC: 30850 AN: 41506

American (AMR) AF: 0.675 AC: 10334 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 2407 AN: 3466

East Asian (EAS) AF: 0.477 AC: 2463 AN: 5166

South Asian (SAS) AF: 0.692 AC: 3337 AN: 4820

European-Finnish (FIN) AF: 0.592 AC: 6259 AN: 10580

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.559 AC: 37987 AN: 67898

Other (OTH) AF: 0.629 AC: 1329 AN: 2112

Bravo AF: 0.637

EpiCase AF: 0.574

EpiControl AF: 0.570

ClinVar

ClinVar submissions as Germline

Significance: 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	-0.80
CADD	Benign	0.98
DANN	Benign	0.80
PhyloP100		-0.50

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000021
dbscSNV1_RF	Benign	0.0
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

Other links and lift over

dbSNP: rs6644951; hg19: chrX-1506318; COSMIC: COSV58429598; COSMIC: COSV58429598;