chr14-36711480-T-C

Variant names:

• chr14-36711480-T-C
• rs17105087
• NM_030631.4:c.441A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 2P and 16B. PP3_Moderate BP6_Very_Strong BA1

The NM_030631.4(SLC25A21):​c.441A>G​(p.Gln147Gln) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0866 in 1,613,042 control chromosomes in the GnomAD database, including 11,499 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1298 hom., cov: 32)
  • Exomes 𝑓: 0.085 (10201 hom.)
• Consequence: SLC25A21 NM_030631.4 splice_region, synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.08
• Publications: 11 publications found

Genes affected

SLC25A21 (HGNC:14411): (solute carrier family 25 member 21) SLC25A21 is a homolog of the S. cerevisiae ODC proteins, mitochondrial carriers that transport C5-C7 oxodicarboxylates across inner mitochondrial membranes. One of the species transported by ODC is 2-oxoadipate, a common intermediate in the catabolism of lysine, tryptophan, and hydroxylysine in mammals. Within mitochondria, 2-oxoadipate is converted into acetyl-CoA.[supplied by OMIM, Apr 2004]

SLC25A21 Gene-Disease associations (from GenCC):

• mitochondrial DNA depletion syndrome 18

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BP6: Variant 14-36711480-T-C is Benign according to our data. Variant chr14-36711480-T-C is described in ClinVar as Benign. ClinVar VariationId is 1332980.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A21	NM_030631.4	c.441A>G	p.Gln147Gln	splice_region_variant, synonymous_variant	Exon 7 of 10	ENST00000331299.6	NP_085134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A21	ENST00000331299.6	c.441A>G	p.Gln147Gln	splice_region_variant, synonymous_variant	Exon 7 of 10	1	NM_030631.4	ENSP00000329452.5
SLC25A21	ENST00000555449.5	c.441A>G	p.Gln147Gln	splice_region_variant, synonymous_variant	Exon 7 of 11	2		ENSP00000451873.1
SLC25A21	ENST00000556444.1	n.113A>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15536 AN: 152010 Hom.: 1295 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0912

Gnomad AMR AF: 0.0960

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0604

Gnomad OTH AF: 0.104

GnomAD2 exomes AF: 0.129 AC: 32343 AN: 250256 AF XY: 0.130

Gnomad AFR exome AF: 0.110

Gnomad AMR exome AF: 0.108

Gnomad ASJ exome AF: 0.140

Gnomad EAS exome AF: 0.500

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.0624

Gnomad OTH exome AF: 0.109

GnomAD4 exome AF: 0.0849 AC: 124090 AN: 1460914 Hom.: 10201 Cov.: 31 AF XY: 0.0884 AC XY: 64231 AN XY: 726732

African (AFR) AF: 0.112 AC: 3744 AN: 33432

American (AMR) AF: 0.105 AC: 4690 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 3536 AN: 26080

East Asian (EAS) AF: 0.480 AC: 19033 AN: 39674

South Asian (SAS) AF: 0.206 AC: 17768 AN: 86084

European-Finnish (FIN) AF: 0.0974 AC: 5198 AN: 53388

Middle Eastern (MID) AF: 0.134 AC: 775 AN: 5764

European-Non Finnish (NFE) AF: 0.0565 AC: 62831 AN: 1111516

Other (OTH) AF: 0.108 AC: 6515 AN: 60332

GnomAD4 genome AF: 0.102 AC: 15558 AN: 152128 Hom.: 1298 Cov.: 32 AF XY: 0.109 AC XY: 8077 AN XY: 74368

African (AFR) AF: 0.107 AC: 4441 AN: 41522

American (AMR) AF: 0.0960 AC: 1466 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 482 AN: 3468

East Asian (EAS) AF: 0.487 AC: 2512 AN: 5154

South Asian (SAS) AF: 0.233 AC: 1121 AN: 4818

European-Finnish (FIN) AF: 0.101 AC: 1071 AN: 10580

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0604 AC: 4109 AN: 67994

Other (OTH) AF: 0.111 AC: 234 AN: 2114

Alfa AF: 0.0786 Hom.: 1433

Bravo AF: 0.103

Asia WGS AF: 0.331 AC: 1148 AN: 3476

EpiCase AF: 0.0652

EpiControl AF: 0.0665

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mitochondrial DNA depletion syndrome 18 Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	20
DANN	Benign	0.42
PhyloP100		2.1
Mutation Taster		=92/8	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.86		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.86		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17105087; hg19: chr14-37180685; COSMIC: COSV58728182;