rs150888153

Variant names:

• chr3-140963071-T-A
• rs150888153
• NM_001104647.3:c.285-56T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.679
• Publications: 2 publications found

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

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001104647.3. 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
	SLC25A36	NM_001104647.3	MANE Select	c.285-56T>A		intron	N/A	NP_001098117.1
	SLC25A36	NM_018155.3		c.285-56T>A		intron	N/A	NP_060625.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A36	ENST00000324194.12	TSL:1 MANE Select	c.285-56T>A		intron	N/A	ENSP00000320688.6
	SLC25A36	ENST00000507429.5	TSL:1	c.285-56T>A		intron	N/A	ENSP00000421470.1
	SLC25A36	ENST00000502594.5	TSL:1	n.285-56T>A		intron	N/A	ENSP00000423319.1

Frequencies

GnomAD3 genomes AF: 0.0137 AC: 2083 AN: 151996 Hom.: 21 Cov.: 32

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

African (AFR) AF: 0.00318 AC: 63 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: 1 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: 94 AN: 4246

European-Non Finnish (NFE) AF: 0.0220 AC: 15491 AN: 703444

Other (OTH) AF: 0.0150 AC: 622 AN: 41586

GnomAD4 genome AF: 0.0137 AC: 2081 AN: 152114 Hom.: 21 Cov.: 32 AF XY: 0.0134 AC XY: 995 AN XY: 74382

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: 59 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4830

European-Finnish (FIN) AF: 0.0155 AC: 164 AN: 10582

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0218 AC: 1478 AN: 67878

Other (OTH) AF: 0.0161 AC: 34 AN: 2112

Alfa AF: 0.0180 Hom.: 2

Bravo AF: 0.0131

Asia WGS AF: 0.00232 AC: 8 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.3
DANN	Benign	0.27
PhyloP100		0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs150888153; hg19: chr3-140681913;