14-37172300-G-T

Variant names:

• chr14-37172300-G-T
• rs775569926
• NM_030631.4:c.51C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_030631.4(SLC25A21):​c.51C>A​(p.Ile17Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,934 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC25A21 NM_030631.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.43
• Publications: 0 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-AS1 (HGNC:44298): (SLC25A21 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP7: Synonymous conserved (PhyloP=2.43 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030631.4. 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
	SLC25A21	NM_030631.4	MANE Select	c.51C>A	p.Ile17Ile	synonymous	Exon 1 of 10	NP_085134.1	Q9BQT8-1
	SLC25A21	NM_001171170.2		c.51C>A	p.Ile17Ile	synonymous	Exon 1 of 11	NP_001164641.1	Q9BQT8-2
	SLC25A21-AS1	NR_033240.1		n.275G>T		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A21	ENST00000331299.6	TSL:1 MANE Select	c.51C>A	p.Ile17Ile	synonymous	Exon 1 of 10	ENSP00000329452.5	Q9BQT8-1
	SLC25A21	ENST00000555449.5	TSL:2	c.51C>A	p.Ile17Ile	synonymous	Exon 1 of 11	ENSP00000451873.1	Q9BQT8-2
	SLC25A21-AS1	ENST00000556667.1	TSL:6	n.413G>T		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447934 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 718734

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33190

American (AMR) AF: 0.00 AC: 0 AN: 43068

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25770

East Asian (EAS) AF: 0.00 AC: 0 AN: 39056

South Asian (SAS) AF: 0.00 AC: 0 AN: 83578

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52000

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1105716

Other (OTH) AF: 0.00 AC: 0 AN: 59808

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	18
DANN	Benign	0.95
PhyloP100		2.4
PromoterAI		-0.11	Neutral

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: rs775569926; hg19: chr14-37641505;