NM_030780.5:c.391+171T>G

Variant names:

• chr8-103404605-A-C
• rs1865855
• NM_030780.5:c.391+171T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030780.5(SLC25A32):​c.391+171T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 151,952 control chromosomes in the GnomAD database, including 1,303 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1303 hom., cov: 32)
• Consequence: SLC25A32 NM_030780.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.164
• Publications: 4 publications found

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]

SLC25A32 Gene-Disease associations (from GenCC):

• exercise intolerance, riboflavin-responsive

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ENSG00000285982 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 8-103404605-A-C is Benign according to our data. Variant chr8-103404605-A-C is described in ClinVar as Benign. ClinVar VariationId is 1279525.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030780.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A32	NM_030780.5	MANE Select	c.391+171T>G		intron	N/A	NP_110407.2
	SLC25A32	NR_102337.2		n.476-1281T>G		intron	N/A
	SLC25A32	NR_102338.2		n.670+171T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A32	ENST00000297578.9	TSL:1 MANE Select	c.391+171T>G		intron	N/A	ENSP00000297578.4
	ENSG00000285982	ENST00000649416.1		c.238+171T>G		intron	N/A	ENSP00000496817.1
	SLC25A32	ENST00000707124.1		c.460+171T>G		intron	N/A	ENSP00000516752.1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19382 AN: 151834 Hom.: 1295 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.0829

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0937

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.128 AC: 19412 AN: 151952 Hom.: 1303 Cov.: 32 AF XY: 0.128 AC XY: 9532 AN XY: 74254

African (AFR) AF: 0.157 AC: 6512 AN: 41480

American (AMR) AF: 0.147 AC: 2246 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0829 AC: 288 AN: 3472

East Asian (EAS) AF: 0.147 AC: 761 AN: 5162

South Asian (SAS) AF: 0.169 AC: 812 AN: 4816

European-Finnish (FIN) AF: 0.0937 AC: 978 AN: 10438

Middle Eastern (MID) AF: 0.0993 AC: 29 AN: 292

European-Non Finnish (NFE) AF: 0.109 AC: 7394 AN: 67998

Other (OTH) AF: 0.126 AC: 266 AN: 2108

Alfa AF: 0.138 Hom.: 906

Bravo AF: 0.132

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.9
DANN	Benign	0.40
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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: rs1865855; hg19: chr8-104416833;