8-103400407-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_030780.5(SLC25A32):c.*4C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0272 in 1,613,758 control chromosomes in the GnomAD database, including 782 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (59 hom., cov: 33)
  • Exomes 𝑓: 0.028 (723 hom.)
• Consequence: SLC25A32 NM_030780.5 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0170

Genes affected

SLC25A32 (HGNC:29683): (solute carrier family 25 member 32) This gene encodes a member of the P(I/L)W subfamily of mitochondrial carrier family transport proteins. The encoded protein transports folate across the inner mitochondrial membrane. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2013]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 8-103400407-G-A is Benign according to our data. Variant chr8-103400407-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1316181.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0197 (2994/152280) while in subpopulation NFE AF= 0.0321 (2186/68020). AF 95% confidence interval is 0.031. There are 59 homozygotes in gnomad4. There are 1390 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 59 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A32	NM_030780.5	c.*4C>T		3_prime_UTR_variant	7/7	ENST00000297578.9
SLC25A32	NR_102337.2	n.1036C>T		non_coding_transcript_exon_variant	6/6
SLC25A32	NR_102338.2	n.1231C>T		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A32	ENST00000297578.9	c.*4C>T		3_prime_UTR_variant	7/7	1	NM_030780.5	P1

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 2995 AN: 152162 Hom.: 59 Cov.: 33

Gnomad AFR AF: 0.00579

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0190

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00580

Gnomad FIN AF: 0.0145

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0321

Gnomad OTH AF: 0.0230

GnomAD3 exomes AF: 0.0190 AC: 4762 AN: 251240 Hom.: 71 AF XY: 0.0190 AC XY: 2582 AN XY: 135808

Gnomad AFR exome AF: 0.00560

Gnomad AMR exome AF: 0.0136

Gnomad ASJ exome AF: 0.00953

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00722

Gnomad FIN exome AF: 0.0134

Gnomad NFE exome AF: 0.0304

Gnomad OTH exome AF: 0.0217

GnomAD4 exome AF: 0.0280 AC: 40939 AN: 1461478 Hom.: 723 Cov.: 31 AF XY: 0.0274 AC XY: 19910 AN XY: 727042

Gnomad4 AFR exome AF: 0.00475

Gnomad4 AMR exome AF: 0.0144

Gnomad4 ASJ exome AF: 0.00972

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00768

Gnomad4 FIN exome AF: 0.0133

Gnomad4 NFE exome AF: 0.0333

Gnomad4 OTH exome AF: 0.0245

GnomAD4 genome AF: 0.0197 AC: 2994 AN: 152280 Hom.: 59 Cov.: 33 AF XY: 0.0187 AC XY: 1390 AN XY: 74462

Gnomad4 AFR AF: 0.00577

Gnomad4 AMR AF: 0.0190

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00559

Gnomad4 FIN AF: 0.0145

Gnomad4 NFE AF: 0.0321

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0196 Hom.: 23

Bravo AF: 0.0196

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0312

EpiControl AF: 0.0311

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 28, 2021

- -

SLC25A32-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 13, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	7.1
Dann	Benign	0.70

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: rs74934875; hg19: chr8-104412635;