8-103400289-A-T

Position:

• chr8-103400289-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000297578.9(SLC25A32):​c.*122T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,166,646 control chromosomes in the GnomAD database, including 29,585 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4027 hom., cov: 33)
  • Exomes 𝑓: 0.22 (25558 hom.)
• Consequence: SLC25A32 ENST00000297578.9 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.186

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=-0.82).
• BP6: Variant 8-103400289-A-T is Benign according to our data. Variant chr8-103400289-A-T is described in ClinVar as [Benign]. Clinvar id is 1289510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A32	NM_030780.5	c.*122T>A		3_prime_UTR_variant	7/7	ENST00000297578.9	NP_110407.2
SLC25A32	NR_102337.2	n.1154T>A		non_coding_transcript_exon_variant	6/6
SLC25A32	NR_102338.2	n.1349T>A		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A32	ENST00000297578.9	c.*122T>A		3_prime_UTR_variant	7/7	1	NM_030780.5	ENSP00000297578	P1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34056 AN: 152040 Hom.: 4030 Cov.: 33

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.0106

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.240

GnomAD4 exome AF: 0.218 AC: 220796 AN: 1014488 Hom.: 25558 Cov.: 13 AF XY: 0.216 AC XY: 112019 AN XY: 518772

Gnomad4 AFR exome AF: 0.264

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.341

Gnomad4 EAS exome AF: 0.00631

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.221

Gnomad4 NFE exome AF: 0.231

Gnomad4 OTH exome AF: 0.222

GnomAD4 genome AF: 0.224 AC: 34075 AN: 152158 Hom.: 4027 Cov.: 33 AF XY: 0.220 AC XY: 16379 AN XY: 74380

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.0106

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.237

Alfa AF: 0.235 Hom.: 539

Bravo AF: 0.222

Asia WGS AF: 0.0860 AC: 301 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.45
DANN	Benign	0.42

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: rs35225263; hg19: chr8-104412517;