rs2072499

Positions:

• chr1-156199819-A-G
• chr1-156199819-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014655.4(SLC25A44):​c.-13-16A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 1,595,982 control chromosomes in the GnomAD database, including 105,876 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.42 (14916 hom., cov: 31)
  • Exomes 𝑓: 0.35 (90960 hom.)
• Consequence: SLC25A44 NM_014655.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03

Genes affected

SLC25A44 (HGNC:29036): (solute carrier family 25 member 44) SLC25A44 belongs to the SLC25 family of mitochondrial carrier proteins (Haitina et al., 2006 [PubMed 16949250]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A44	NM_014655.4	c.-13-16A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000359511.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A44	ENST00000359511.5	c.-13-16A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_014655.4	P4

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63752 AN: 151800 Hom.: 14873 Cov.: 31

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.404

GnomAD3 exomes AF: 0.336 AC: 80107 AN: 238738 Hom.: 14830 AF XY: 0.331 AC XY: 42402 AN XY: 128266

Gnomad AFR exome AF: 0.644

Gnomad AMR exome AF: 0.286

Gnomad ASJ exome AF: 0.294

Gnomad EAS exome AF: 0.152

Gnomad SAS exome AF: 0.291

Gnomad FIN exome AF: 0.342

Gnomad NFE exome AF: 0.349

Gnomad OTH exome AF: 0.338

GnomAD4 exome AF: 0.349 AC: 503827 AN: 1444064 Hom.: 90960 Cov.: 32 AF XY: 0.346 AC XY: 248084 AN XY: 716980

Gnomad4 AFR exome AF: 0.648

Gnomad4 AMR exome AF: 0.294

Gnomad4 ASJ exome AF: 0.296

Gnomad4 EAS exome AF: 0.160

Gnomad4 SAS exome AF: 0.297

Gnomad4 FIN exome AF: 0.340

Gnomad4 NFE exome AF: 0.354

Gnomad4 OTH exome AF: 0.355

GnomAD4 genome AF: 0.420 AC: 63843 AN: 151918 Hom.: 14916 Cov.: 31 AF XY: 0.413 AC XY: 30686 AN XY: 74254

Gnomad4 AFR AF: 0.633

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.400

Alfa AF: 0.356 Hom.: 20765

Bravo AF: 0.427

Asia WGS AF: 0.243 AC: 847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.36
DANN	Benign	0.37

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: rs2072499; hg19: chr1-156169610;