22-19176064-C-CAT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005984.5(SLC25A1):c.*65_*66insAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.75 (43956 hom., cov: 0)
  • Exomes 𝑓: 0.67 (270203 hom.)
• Consequence: SLC25A1 NM_005984.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.680

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 22-19176064-C-CAT is Benign according to our data. Variant chr22-19176064-C-CAT is described in ClinVar as [Benign]. Clinvar id is 1221291.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A1	NM_005984.5	c.*65_*66insAT		3_prime_UTR_variant	9/9	ENST00000215882.10
SLC25A1	NM_001256534.2	c.*65_*66insAT		3_prime_UTR_variant	8/8
SLC25A1	NM_001287387.2	c.*65_*66insAT		3_prime_UTR_variant	9/9
SLC25A1	NR_046298.3	n.925_926insAT		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A1	ENST00000215882.10	c.*65_*66insAT		3_prime_UTR_variant	9/9	1	NM_005984.5	P1
SLC25A1	ENST00000451283.5	c.*65_*66insAT		3_prime_UTR_variant	9/9	2
SLC25A1	ENST00000470922.5	n.1143_1144insAT		non_coding_transcript_exon_variant	8/8	2

Frequencies

GnomAD3 genomes AF: 0.751 AC: 113663 AN: 151376 Hom.: 43882 Cov.: 0

Gnomad AFR AF: 0.923

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.717

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.719

GnomAD4 exome AF: 0.671 AC: 787237 AN: 1173292 Hom.: 270203 Cov.: 17 AF XY: 0.675 AC XY: 403436 AN XY: 597348

Gnomad4 AFR exome AF: 0.931

Gnomad4 AMR exome AF: 0.818

Gnomad4 ASJ exome AF: 0.647

Gnomad4 EAS exome AF: 0.947

Gnomad4 SAS exome AF: 0.849

Gnomad4 FIN exome AF: 0.653

Gnomad4 NFE exome AF: 0.626

Gnomad4 OTH exome AF: 0.693

GnomAD4 genome AF: 0.751 AC: 113799 AN: 151496 Hom.: 43956 Cov.: 0 AF XY: 0.756 AC XY: 55939 AN XY: 74014

Gnomad4 AFR AF: 0.923

Gnomad4 AMR AF: 0.755

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.942

Gnomad4 SAS AF: 0.856

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.723

Alfa AF: 0.701 Hom.: 4707

Bravo AF: 0.759

Asia WGS AF: 0.902 AC: 3138 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

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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: rs35359423; hg19: chr22-19163577; COSMIC: COSV53205364; COSMIC: COSV53205364;