19-19096308-T-A

Position:

• chr19-19096308-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_178526.5(SLC25A42):​c.81+103T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 646,420 control chromosomes in the GnomAD database, including 209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (141 hom., cov: 0)
  • Exomes 𝑓: 0.0074 (68 hom.)
• Consequence: SLC25A42 NM_178526.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.02

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 19-19096308-T-A is Benign according to our data. Variant chr19-19096308-T-A is described in ClinVar as [Benign]. Clinvar id is 1234690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A42	NM_178526.5	c.81+103T>A		intron_variant		ENST00000318596.8
SLC25A42	NM_001321544.2	c.81+103T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A42	ENST00000318596.8	c.81+103T>A		intron_variant		1	NM_178526.5	P1
SLC25A42	ENST00000594070.5	n.263+103T>A		intron_variant, non_coding_transcript_variant		2
SLC25A42	ENST00000597661.5	n.144+103T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.136 AC: 3813 AN: 27952 Hom.: 138 Cov.: 0

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.00725

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0919

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0216

Gnomad FIN AF: 0.00564

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0281

Gnomad OTH AF: 0.123

GnomAD4 exome AF: 0.00741 AC: 4582 AN: 618402 Hom.: 68 AF XY: 0.00701 AC XY: 2236 AN XY: 318818

Gnomad4 AFR exome AF: 0.0811

Gnomad4 AMR exome AF: 0.00940

Gnomad4 ASJ exome AF: 0.0169

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00426

Gnomad4 FIN exome AF: 0.000523

Gnomad4 NFE exome AF: 0.00514

Gnomad4 OTH exome AF: 0.0125

GnomAD4 genome AF: 0.137 AC: 3831 AN: 28018 Hom.: 141 Cov.: 0 AF XY: 0.131 AC XY: 1803 AN XY: 13722

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.0919

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0203

Gnomad4 FIN AF: 0.00564

Gnomad4 NFE AF: 0.0281

Gnomad4 OTH AF: 0.118

Alfa AF: 0.0149 Hom.: 5

Bravo AF: 0.0288

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 25, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs112968719; hg19: chr19-19207117;