NM_030631.4:c.-207T>C

Variant names:

• chr14-37172557-A-G
• rs56237223
• NM_030631.4:c.-207T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_030631.4(SLC25A21):​c.-207T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00562 in 712,774 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0053 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0057 (26 hom.)
• Consequence: SLC25A21 NM_030631.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.30
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.043).
• BP6: Variant 14-37172557-A-G is Benign according to our data. Variant chr14-37172557-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3777835.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 Unknown,AR gene

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.-207T>C		5_prime_UTR	Exon 1 of 10	NP_085134.1	Q9BQT8-1
	SLC25A21	NM_001171170.2		c.-207T>C		5_prime_UTR	Exon 1 of 11	NP_001164641.1	Q9BQT8-2
	SLC25A21-AS1	NR_033240.1		n.532A>G		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.-207T>C		5_prime_UTR	Exon 1 of 10	ENSP00000329452.5	Q9BQT8-1
	SLC25A21-AS1	ENST00000556667.1	TSL:6	n.670A>G		non_coding_transcript_exon	Exon 1 of 1
	SLC25A21	ENST00000555449.5	TSL:2	c.-207T>C		upstream_gene	N/A	ENSP00000451873.1	Q9BQT8-2

Frequencies

GnomAD3 genomes AF: 0.00531 AC: 808 AN: 152212 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0211

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00757

Gnomad OTH AF: 0.00334

GnomAD2 exomes AF: 0.00395 AC: 547 AN: 138418 AF XY: 0.00373

Gnomad AFR exome AF: 0.000771

Gnomad AMR exome AF: 0.00102

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0197

Gnomad NFE exome AF: 0.00561

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00570 AC: 3195 AN: 560444 Hom.: 26 Cov.: 5 AF XY: 0.00553 AC XY: 1675 AN XY: 302882

African (AFR) AF: 0.000503 AC: 8 AN: 15910

American (AMR) AF: 0.00144 AC: 50 AN: 34650

Ashkenazi Jewish (ASJ) AF: 0.0000499 AC: 1 AN: 20026

East Asian (EAS) AF: 0.00 AC: 0 AN: 32026

South Asian (SAS) AF: 0.00264 AC: 164 AN: 62124

European-Finnish (FIN) AF: 0.0185 AC: 663 AN: 35900

Middle Eastern (MID) AF: 0.000491 AC: 2 AN: 4076

European-Non Finnish (NFE) AF: 0.00652 AC: 2118 AN: 324970

Other (OTH) AF: 0.00614 AC: 189 AN: 30762

GnomAD4 genome AF: 0.00530 AC: 808 AN: 152330 Hom.: 4 Cov.: 33 AF XY: 0.00534 AC XY: 398 AN XY: 74484

African (AFR) AF: 0.000553 AC: 23 AN: 41588

American (AMR) AF: 0.00209 AC: 32 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4828

European-Finnish (FIN) AF: 0.0211 AC: 224 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00757 AC: 515 AN: 68028

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.00490 Hom.: 1

Bravo AF: 0.00321

Asia WGS AF: 0.000577 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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	-0.98
CADD	Benign	0.081
DANN	Benign	0.32
PhyloP100		-4.3
PromoterAI		0.042	Neutral
Mutation Taster		=300/0	polymorphism

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: rs56237223; hg19: chr14-37641762;