chr3-140957958-C-T

Variant names:

• chr3-140957958-C-T
• rs141220432
• NM_001104647.3:c.206+1267C>T

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.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
• Publications: 0 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: STRONG, LIMITED Submitted by: Ambry Genetics, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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 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.206+1267C>T		intron	N/A	NP_001098117.1	A0A384MEA9
	SLC25A36	NM_018155.3		c.206+1267C>T		intron	N/A	NP_060625.2	Q96CQ1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A36	ENST00000324194.12	TSL:1 MANE Select	c.206+1267C>T		intron	N/A	ENSP00000320688.6	Q96CQ1-1
	SLC25A36	ENST00000507429.5	TSL:1	c.206+1267C>T		intron	N/A	ENSP00000421470.1	F6SDC8
	SLC25A36	ENST00000502594.5	TSL:1	n.206+1267C>T		intron	N/A	ENSP00000423319.1	Q96CQ1-2

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

African (AFR) AF: 0.00345 AC: 143 AN: 41460

American (AMR) AF: 0.0105 AC: 160 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0171 AC: 59 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00291 AC: 14 AN: 4816

European-Finnish (FIN) AF: 0.0155 AC: 164 AN: 10576

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

European-Non Finnish (NFE) AF: 0.0219 AC: 1487 AN: 67982

Other (OTH) AF: 0.0161 AC: 34 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.3
DANN	Benign	0.59
PhyloP100		0.15
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: rs141220432; hg19: chr3-140676800;