22-19175882-A-AGGCACAGGGTTCACAGTAAGCACATGGACAAGTG

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_005984.5(SLC25A1):c.*247_*248insCACTTGTCCATGTGCTTACTGTGAACCCTGTGCC 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 (44094 hom., cov: 0)
  • Exomes 𝑓: 0.70 (88741 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC25A1 NM_005984.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.172

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 Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 22-19175882-A-AGGCACAGGGTTCACAGTAAGCACATGGACAAGTG is Benign according to our data. Variant chr22-19175882-A-AGGCACAGGGTTCACAGTAAGCACATGGACAAGTG is described in ClinVar as [Benign]. Clinvar id is 1342728.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A1	NM_005984.5	c.*247_*248insCACTTGTCCATGTGCTTACTGTGAACCCTGTGCC		3_prime_UTR_variant	9/9	ENST00000215882.10
SLC25A1	NM_001256534.2	c.*247_*248insCACTTGTCCATGTGCTTACTGTGAACCCTGTGCC		3_prime_UTR_variant	8/8
SLC25A1	NM_001287387.2	c.*247_*248insCACTTGTCCATGTGCTTACTGTGAACCCTGTGCC		3_prime_UTR_variant	9/9
SLC25A1	NR_046298.3	n.1107_1108insCACTTGTCCATGTGCTTACTGTGAACCCTGTGCC		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A1	ENST00000215882.10	c.*247_*248insCACTTGTCCATGTGCTTACTGTGAACCCTGTGCC		3_prime_UTR_variant	9/9	1	NM_005984.5	P1
SLC25A1	ENST00000451283.5	c.*247_*248insCACTTGTCCATGTGCTTACTGTGAACCCTGTGCC		3_prime_UTR_variant	9/9	2
SLC25A1	ENST00000470922.5	n.1325_1326insCACTTGTCCATGTGCTTACTGTGAACCCTGTGCC		non_coding_transcript_exon_variant	8/8	2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 113752 AN: 151352 Hom.: 44024 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.920

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.940

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.722

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.698 AC: 247607 AN: 354616 Hom.: 88741 Cov.: 0 AF XY: 0.706 AC XY: 131561 AN XY: 186292

Gnomad4 AFR exome AF: 0.915

Gnomad4 AMR exome AF: 0.774

Gnomad4 ASJ exome AF: 0.664

Gnomad4 EAS exome AF: 0.941

Gnomad4 SAS exome AF: 0.847

Gnomad4 FIN exome AF: 0.648

Gnomad4 NFE exome AF: 0.631

Gnomad4 OTH exome AF: 0.697

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.752 AC: 113883 AN: 151472 Hom.: 44094 Cov.: 0 AF XY: 0.756 AC XY: 55943 AN XY: 73972

Gnomad4 AFR AF: 0.920

Gnomad4 AMR AF: 0.754

Gnomad4 ASJ AF: 0.678

Gnomad4 EAS AF: 0.940

Gnomad4 SAS AF: 0.856

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.645

Gnomad4 OTH AF: 0.726

Alfa AF: 0.407 Hom.: 990

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

Feb 28, 2022

- -

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: rs147828180; hg19: chr22-19163395;