chrX-1389464-C-G

Variant names:

• chrX-1389464-C-G
• rs17848744
• NM_001636.4:c.375G>C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001636.4(SLC25A6):​c.375G>C​(p.Ala125Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000395 in 1,613,916 control chromosomes in the GnomAD database, including 4 homozygotes. There are 345 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A125A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00034 (1 hom., 32 hem., cov: 32)
  • Exomes 𝑓: 0.00040 (3 hom. 313 hem.)
• Consequence: SLC25A6 NM_001636.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.08
• 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=3.08 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 32 gene

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.375G>C	p.Ala125Ala	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.375G>C	p.Ala125Ala	synonymous	Exon 2 of 4	ENSP00000370808.5	P12236
	SLC25A6	ENST00000871943.1		c.375G>C	p.Ala125Ala	synonymous	Exon 2 of 4	ENSP00000542002.1
	SLC25A6	ENST00000871942.1		c.375G>C	p.Ala125Ala	synonymous	Exon 3 of 5	ENSP00000542001.1

Frequencies

GnomAD3 genomes AF: 0.000342 AC: 52 AN: 152206 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00847

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000748 AC: 188 AN: 251330 AF XY: 0.000751

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00761

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000401 AC: 586 AN: 1461592 Hom.: 3 Cov.: 38 AF XY: 0.000430 AC XY: 313 AN XY: 727090

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0113 AC: 447 AN: 39700

South Asian (SAS) AF: 0.00141 AC: 122 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5668

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111906

Other (OTH) AF: 0.000232 AC: 14 AN: 60364

GnomAD4 genome AF: 0.000341 AC: 52 AN: 152324 Hom.: 1 Cov.: 32 AF XY: 0.000430 AC XY: 32 AN XY: 74486

African (AFR) AF: 0.00 AC: 0 AN: 41576

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00849 AC: 44 AN: 5184

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Bravo AF: 0.000408

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	8.0
DANN	Benign	0.40
PhyloP100		3.1
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs17848744; hg19: chrX-1508357; COSMIC: COSV67317655;