19-19096212-A-ACCCCGGCCTCCTGGGATGGGTGTTCTCCTGGGG

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_178526.5(SLC25A42):c.81+12_81+44dup variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00063 in 1,603,944 control chromosomes in the GnomAD database, including 12 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00036 (7 hom.)
• Consequence: SLC25A42 NM_178526.5 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00500

Genes affected

SLC25A42 (HGNC:28380): (solute carrier family 25 member 42) This gene encodes a solute carrier family 25 protein. Solute carrier family 25 proteins are localized to mitochondria and play critical roles in the transport of molecules across the inner mitochondrial membrane. The encoded protein is a mitochondrial transporter for coenzyme A (CoA) and adenosine 3',5'-diphosphate. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 19-19096212-A-ACCCCGGCCTCCTGGGATGGGTGTTCTCCTGGGG is Benign according to our data. Variant chr19-19096212-A-ACCCCGGCCTCCTGGGATGGGTGTTCTCCTGGGG is described in ClinVar as [Benign]. Clinvar id is 1606383.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A42	NM_178526.5	c.81+12_81+44dup		splice_region_variant, intron_variant		ENST00000318596.8
SLC25A42	NM_001321544.2	c.81+12_81+44dup		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A42	ENST00000318596.8	c.81+12_81+44dup		splice_region_variant, intron_variant		1	NM_178526.5	P1
SLC25A42	ENST00000594070.5	n.263+12_263+44dup		splice_region_variant, intron_variant, non_coding_transcript_variant		2
SLC25A42	ENST00000597661.5	n.144+12_144+44dup		splice_region_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00322 AC: 486 AN: 151064 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000527

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000590

Gnomad OTH AF: 0.00193

GnomAD3 exomes AF: 0.000845 AC: 211 AN: 249642 Hom.: 0 AF XY: 0.000644 AC XY: 87 AN XY: 135018

Gnomad AFR exome AF: 0.0119

Gnomad AMR exome AF: 0.000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000981

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000355

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000361 AC: 525 AN: 1452760 Hom.: 7 Cov.: 31 AF XY: 0.000316 AC XY: 228 AN XY: 720762

Gnomad4 AFR exome AF: 0.0129

Gnomad4 AMR exome AF: 0.000359

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000172

Gnomad4 OTH exome AF: 0.000802

GnomAD4 genome AF: 0.00321 AC: 486 AN: 151184 Hom.: 5 Cov.: 32 AF XY: 0.00282 AC XY: 208 AN XY: 73870

Gnomad4 AFR AF: 0.0114

Gnomad4 AMR AF: 0.000526

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000590

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.000668 Hom.: 0

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0000546

EpiControl AF: 0.0000593

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

Invitae

Jan 26, 2024

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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: rs547409543; hg19: chr19-19207021;