rs141220432

Positions:

• chr3-140957958-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001104647.3(SLC25A36):​c.206+1267C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 152,074 control chromosomes in the GnomAD database, including 21 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)
• Consequence: SLC25A36 NM_001104647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0137 (2091/152074) while in subpopulation NFE AF= 0.0219 (1487/67982). AF 95% confidence interval is 0.0209. There are 21 homozygotes in gnomad4. There are 996 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A36	NM_001104647.3	c.206+1267C>T		intron_variant		ENST00000324194.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A36	ENST00000324194.12	c.206+1267C>T		intron_variant		1	NM_001104647.3	P3

Frequencies

GnomAD3 genomes AF: 0.0138 AC: 2093 AN: 151956 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.00346

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.0171

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.0155

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0219

Gnomad OTH AF: 0.0163

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0137 AC: 2091 AN: 152074 Hom.: 21 Cov.: 32 AF XY: 0.0134 AC XY: 996 AN XY: 74336

Gnomad4 AFR AF: 0.00345

Gnomad4 AMR AF: 0.0105

Gnomad4 ASJ AF: 0.0171

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00291

Gnomad4 FIN AF: 0.0155

Gnomad4 NFE AF: 0.0219

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.0181 Hom.: 2

Bravo AF: 0.0132

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.3
DANN	Benign	0.59

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

LitVar

Other links and lift over

dbSNP: rs141220432; hg19: chr3-140676800;