Genetic Variant NM_001151.4:c.111+146_111+149dupCCGC (chr4-185143605-G-GCGCC) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_001151.4(SLC25A4):c.111+146_111+149dupCCGC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC25A4
NM_001151.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.378

Publications

4 publications found

Variant links:

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

SLC25A4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000135 (19/140724) while in subpopulation EAS AF = 0.000627 (3/4788). AF 95% confidence interval is 0.000171. There are 0 homozygotes in GnomAd4. There are 7 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 link	c.111+146_111+149dupCCGC		intron_variant	Intron 1 of 3	ENST00000281456.11	NP_001142.2	P12235A0A0S2Z3H3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A4	ENST00000281456.11 link	c.111+146_111+149dupCCGC		intron_variant	Intron 1 of 3	1	NM_001151.4	ENSP00000281456.5		P12235
SLC25A4	ENST00000491736.1 link	n.111+146_111+149dupCCGC		intron_variant	Intron 1 of 3	5		ENSP00000476711.1		V9GYG0

Frequencies

GnomAD3 genomes

AF:

0.000135

AC:

AN:

140724

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000549

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000275

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000627

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000115

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000612

Gnomad OTH

AF:

0.00255

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

7556

Hom.:

AF XY:

0.00

AC XY:

AN XY:

3854

African (AFR)

AF:

0.00

AC:

AN:

202

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

152

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

6532

Other (OTH)

AF:

0.00

AC:

AN:

262

GnomAD4 genome

AF:

0.000135

AC:

AN:

140724

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

68442

show subpopulations

African (AFR)

AF:

0.0000549

AC:

AN:

36448

American (AMR)

AF:

0.000275

AC:

AN:

14558

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3366

East Asian (EAS)

AF:

0.000627

AC:

AN:

4788

South Asian (SAS)

AF:

0.00

AC:

AN:

4374

European-Finnish (FIN)

AF:

0.000115

AC:

AN:

8704

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.0000612

AC:

AN:

65362

Other (OTH)

AF:

0.00255

AC:

AN:

1960

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

816

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.38

Splicing

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

Publications

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NM_001151.4:c.111+146_111+149dupCCGC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over