NM_001151.4:c.-103C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_001151.4(SLC25A4):c.-103C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000996 in 624,466 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 3 hom. )

Consequence

SLC25A4
NM_001151.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.59

Publications

0 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: PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2
Inheritance: AD Classification: STRONG, MODERATE Submitted by: PanelApp Australia, 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 4-185143270-C-T is Benign according to our data. Variant chr4-185143270-C-T is described in ClinVar as Benign. ClinVar VariationId is 348242.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000862 (131/151988) while in subpopulation AMR AF = 0.00183 (28/15278). AF 95% confidence interval is 0.0013. There are 0 homozygotes in GnomAd4. There are 71 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 3 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001151.4. 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
	SLC25A4	NM_001151.4	MANE Select	c.-103C>T		5_prime_UTR	Exon 1 of 4	NP_001142.2	A0A0S2Z3H3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC25A4	ENST00000281456.11	TSL:1 MANE Select	c.-103C>T	5_prime_UTR	Exon 1 of 4	ENSP00000281456.5	P12235
SLC25A4	ENST00000948444.1		c.-103C>T	5_prime_UTR	Exon 1 of 4	ENSP00000618503.1
SLC25A4	ENST00000948442.1		c.-103C>T	5_prime_UTR	Exon 1 of 4	ENSP00000618501.1

Frequencies

GnomAD3 genomes

AF:

0.000863

AC:

131

AN:

151880

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00184

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00132

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00104

AC:

491

AN:

472478

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

266

AN XY:

257984

show subpopulations

African (AFR)

AF:

0.000424

AC:

AN:

9430

American (AMR)

AF:

0.000287

AC:

AN:

24418

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14438

East Asian (EAS)

AF:

0.00

AC:

AN:

20878

South Asian (SAS)

AF:

0.00

AC:

AN:

52644

European-Finnish (FIN)

AF:

0.000584

AC:

AN:

42788

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2516

European-Non Finnish (NFE)

AF:

0.00150

AC:

423

AN:

281796

Other (OTH)

AF:

0.00136

AC:

AN:

23570

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

100

125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000862

AC:

131

AN:

151988

Hom.:

Cov.:

AF XY:

0.000956

AC XY:

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41508

American (AMR)

AF:

0.00183

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5102

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.000378

AC:

AN:

10576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00133

AC:

AN:

67922

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000318

Hom.:

Bravo

AF:

0.000820

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

2.6

PromoterAI

0.34

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=300/0

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over