22-19176063-T-TCA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_005984.5(SLC25A1):c.*66_*67insTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00826 in 947,492 control chromosomes in the GnomAD database, including 55 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (2 hom., cov: 34)
  • Exomes 𝑓: 0.0079 (53 hom.)
• Consequence: SLC25A1 NM_005984.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.466

Genes affected

SLC25A1 (HGNC:10979): (solute carrier family 25 member 1) This gene encodes a member of the mitochondrial carrier subfamily of solute carrier proteins. Members of this family include nuclear-encoded transporters that translocate small metabolites across the mitochondrial membrane. This protein regulates the movement of citrate across the inner membranes of the mitochondria. Mutations in this gene have been associated with combined D-2- and L-2-hydroxyglutaric aciduria. Pseudogenes of this gene have been identified on chromosomes 7, 11, 16, and 19. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 22-19176063-T-TCA is Benign according to our data. Variant chr22-19176063-T-TCA is described in ClinVar as [Likely_benign]. Clinvar id is 1327332.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0133 (839/62976) while in subpopulation AMR AF= 0.0126 (80/6336). AF 95% confidence interval is 0.0104. There are 2 homozygotes in gnomad4. There are 448 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A1	NM_005984.5	c.*66_*67insTG		3_prime_UTR_variant	9/9	ENST00000215882.10
SLC25A1	NM_001256534.2	c.*66_*67insTG		3_prime_UTR_variant	8/8
SLC25A1	NM_001287387.2	c.*66_*67insTG		3_prime_UTR_variant	9/9
SLC25A1	NR_046298.3	n.926_927insTG		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A1	ENST00000215882.10	c.*66_*67insTG		3_prime_UTR_variant	9/9	1	NM_005984.5	P1
SLC25A1	ENST00000451283.5	c.*66_*67insTG		3_prime_UTR_variant	9/9	2
SLC25A1	ENST00000470922.5	n.1144_1145insTG		non_coding_transcript_exon_variant	8/8	2

Frequencies

GnomAD3 genomes AF: 0.0133 AC: 839 AN: 63002 Hom.: 2 Cov.: 34

Gnomad AFR AF: 0.00605

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0126

Gnomad ASJ AF: 0.0244

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00825

Gnomad FIN AF: 0.0373

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0110

Gnomad OTH AF: 0.0154

GnomAD4 exome AF: 0.00790 AC: 6990 AN: 884516 Hom.: 53 Cov.: 16 AF XY: 0.00789 AC XY: 3593 AN XY: 455184

Gnomad4 AFR exome AF: 0.00125

Gnomad4 AMR exome AF: 0.00282

Gnomad4 ASJ exome AF: 0.0155

Gnomad4 EAS exome AF: 0.0000337

Gnomad4 SAS exome AF: 0.00295

Gnomad4 FIN exome AF: 0.0232

Gnomad4 NFE exome AF: 0.00806

Gnomad4 OTH exome AF: 0.00735

GnomAD4 genome AF: 0.0133 AC: 839 AN: 62976 Hom.: 2 Cov.: 34 AF XY: 0.0148 AC XY: 448 AN XY: 30206

Gnomad4 AFR AF: 0.00605

Gnomad4 AMR AF: 0.0126

Gnomad4 ASJ AF: 0.0244

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00828

Gnomad4 FIN AF: 0.0373

Gnomad4 NFE AF: 0.0110

Gnomad4 OTH AF: 0.0154

Bravo AF: 0.00424

Asia WGS AF: 0.00110 AC: 3 AN: 2748

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 01, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs72564416; hg19: chr22-19163576;