dbSNP rs150888153: SLC25A36:c.285-56T>A (chr3-140963071-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001104647.3(SLC25A36):c.285-56T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.018 in 1,094,584 control chromosomes in the GnomAD database, including 216 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.014 ( 21 hom., cov: 32)

Exomes 𝑓: 0.019 ( 195 hom. )

Consequence

SLC25A36
NM_001104647.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.679

Publications

2 publications found

Variant links:

Genes affected

SLC25A36 (HGNC:25554): (solute carrier family 25 member 36) Enables pyrimidine nucleotide transmembrane transporter activity. Involved in mitochondrial genome maintenance; pyrimidine nucleotide transport; and regulation of mitochondrial membrane potential. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

SLC25A36 Gene-Disease associations (from GenCC):

hyperinsulinemic hypoglycemia, familial, 8
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

SLC25A36 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=-0.81).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0137 (2081/152114) while in subpopulation NFE AF = 0.0218 (1478/67878). AF 95% confidence interval is 0.0209. There are 21 homozygotes in GnomAd4. There are 995 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A36	NM_001104647.3 link	c.285-56T>A		intron_variant	Intron 3 of 6	ENST00000324194.12	NP_001098117.1	Q96CQ1-1A0A384MEA9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A36	ENST00000324194.12 link	c.285-56T>A		intron_variant	Intron 3 of 6	1	NM_001104647.3	ENSP00000320688.6		Q96CQ1-1

Frequencies

GnomAD3 genomes

AF:

0.0137

AC:

2083

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00343

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.0105

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.0155

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0218

Gnomad OTH

AF:

0.0163

GnomAD4 exome

AF:

0.0187

AC:

17664

AN:

942470

Hom.:

195

AF XY:

0.0184

AC XY:

8879

AN XY:

482586

show subpopulations

African (AFR)

AF:

0.00318

AC:

AN:

19830

American (AMR)

AF:

0.0110

AC:

248

AN:

22538

Ashkenazi Jewish (ASJ)

AF:

0.0152

AC:

287

AN:

18828

East Asian (EAS)

AF:

0.0000301

AC:

AN:

33212

South Asian (SAS)

AF:

0.00193

AC:

110

AN:

56886

European-Finnish (FIN)

AF:

0.0179

AC:

748

AN:

41900

Middle Eastern (MID)

AF:

0.0221

AC:

AN:

4246

European-Non Finnish (NFE)

AF:

0.0220

AC:

15491

AN:

703444

Other (OTH)

AF:

0.0150

AC:

622

AN:

41586

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

831

1662

2493

3324

4155

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

492

984

1476

1968

2460

<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:

0.0137

AC:

2081

AN:

152114

Hom.:

Cov.:

AF XY:

0.0134

AC XY:

995

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.00342

AC:

142

AN:

41572

American (AMR)

AF:

0.0105

AC:

160

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0170

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00290

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0155

AC:

164

AN:

10582

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0218

AC:

1478

AN:

67878

Other (OTH)

AF:

0.0161

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

109

219

328

438

547

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0180

Hom.:

Bravo

AF:

0.0131

Asia WGS

AF:

0.00232

AC:

AN:

3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.3

(source)

DANN

Benign

0.27

PhyloP100

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over