rs143715129

Variant names:

• chr4-185143605-GCGCCCGCCCGCCCGCC-G
• rs143715129
• NM_001151.4:c.111+134_111+149delCCGCCCGCCCGCCCGC

Your query was ambiguous. Multiple possible variants found:

• chr4-185143605-GCGCCCGCCCGCCCGCC-G
• chr4-185143605-GCGCCCGCCCGCCCGCC-GCGCC
• chr4-185143605-GCGCCCGCCCGCCCGCC-GCGCCCGCC
• chr4-185143605-GCGCCCGCCCGCCCGCC-GCGCCCGCCCGCC
• chr4-185143605-GCGCCCGCCCGCCCGCC-GCGCCCGCCCGCCCGCCCGCC
• chr4-185143605-GCGCCCGCCCGCCCGCC-GCGCCCGCCCGCCCGCCCGCCCGCC
• chr4-185143605-GCGCCCGCCCGCCCGCC-GCGCCCGCCCGCCCGCCCGCCCGCCCGCC
• chr4-185143605-GCGCCCGCCCGCCCGCC-GCGCCCGCCCGCCCGCCCGCCCGCCCGCCCGCC
• chr4-185143605-GCGCCCGCCCGCCCGCC-GCGCCCGCCCGCCCGCCCGCCCGCCCGCCCGCCCGCC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_001151.4(SLC25A4):​c.111+134_111+149delCCGCCCGCCCGCCCGC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 148,378 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00040 (0 hom.)
• Consequence: SLC25A4 NM_001151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 4 publications found

Genes affected

SLC25A4 (HGNC:10990): (solute carrier family 25 member 4) 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 forms a homodimer embedded in the inner mitochondria membrane. Mutations in this gene have been shown to result in autosomal dominant progressive external opthalmoplegia and familial hypertrophic cardiomyopathy. [provided by RefSeq, Jun 2013]

SLC25A4 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• mitochondrial DNA depletion syndrome 12B (cardiomyopathic type), autosomal recessive

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• Fontaine progeroid syndrome

  Inheritance: AD Classification: STRONG Submitted by: G2P
• mitochondrial DNA depletion syndrome 12A (cardiomyopathic type), autosomal dominant

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal dominant progressive external ophthalmoplegia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Sengers syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00111 (157/140822) while in subpopulation AFR AF = 0.00254 (93/36548). AF 95% confidence interval is 0.00213. There are 0 homozygotes in GnomAd4. There are 81 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A4	NM_001151.4	c.111+134_111+149delCCGCCCGCCCGCCCGC		intron_variant	Intron 1 of 3	ENST00000281456.11	NP_001142.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A4	ENST00000281456.11	c.111+134_111+149delCCGCCCGCCCGCCCGC		intron_variant	Intron 1 of 3	1	NM_001151.4	ENSP00000281456.5
SLC25A4	ENST00000491736.1	n.111+134_111+149delCCGCCCGCCCGCCCGC		intron_variant	Intron 1 of 3	5		ENSP00000476711.1

Frequencies

GnomAD3 genomes AF: 0.00112 AC: 157 AN: 140726 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00255

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000687

Gnomad ASJ AF: 0.00564

Gnomad EAS AF: 0.000209

Gnomad SAS AF: 0.000229

Gnomad FIN AF: 0.000230

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000398

Gnomad OTH AF: 0.00255

GnomAD4 exome AF: 0.000397 AC: 3 AN: 7556 Hom.: 0 AF XY: 0.000519 AC XY: 2 AN XY: 3854

African (AFR) AF: 0.00495 AC: 1 AN: 202

American (AMR) AF: 0.00 AC: 0 AN: 40

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 72

East Asian (EAS) AF: 0.00 AC: 0 AN: 52

South Asian (SAS) AF: 0.00 AC: 0 AN: 230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 152

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 14

European-Non Finnish (NFE) AF: 0.000153 AC: 1 AN: 6532

Other (OTH) AF: 0.00382 AC: 1 AN: 262

GnomAD4 genome AF: 0.00111 AC: 157 AN: 140822 Hom.: 0 Cov.: 0 AF XY: 0.00118 AC XY: 81 AN XY: 68546

African (AFR) AF: 0.00254 AC: 93 AN: 36548

American (AMR) AF: 0.000686 AC: 10 AN: 14582

Ashkenazi Jewish (ASJ) AF: 0.00564 AC: 19 AN: 3366

East Asian (EAS) AF: 0.000210 AC: 1 AN: 4772

South Asian (SAS) AF: 0.000229 AC: 1 AN: 4368

European-Finnish (FIN) AF: 0.000230 AC: 2 AN: 8704

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 262

European-Non Finnish (NFE) AF: 0.000398 AC: 26 AN: 65352

Other (OTH) AF: 0.00252 AC: 5 AN: 1984

Alfa AF: 0.000310 Hom.: 816

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs143715129; hg19: chr4-186064759;