10-99619523-A-G

Position:

• chr10-99619523-A-G

Variant summary

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

The NM_031212.4(SLC25A28):​c.291+522T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.868 in 649,980 control chromosomes in the GnomAD database, including 245,307 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 0.85 (54847 hom., cov: 33)
  • Exomes 𝑓: 0.87 (190460 hom.)
• Consequence: SLC25A28 NM_031212.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.809

Genes affected

SLC25A28 (HGNC:23472): (solute carrier family 25 member 28) Predicted to enable ferrous iron transmembrane transporter activity. Predicted to be involved in iron import into the mitochondrion. Predicted to be located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

SLC25A28 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A28	NM_031212.4	c.291+522T>C		intron_variant		ENST00000370495.6	NP_112489.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A28	ENST00000370495.6	c.291+522T>C		intron_variant		1	NM_031212.4	ENSP00000359526.4

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128901 AN: 152110 Hom.: 54808 Cov.: 33

Gnomad AFR AF: 0.782

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.830

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.875

Gnomad FIN AF: 0.889

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.878

Gnomad OTH AF: 0.855

GnomAD4 exome AF: 0.874 AC: 434980 AN: 497752 Hom.: 190460 AF XY: 0.873 AC XY: 204438 AN XY: 234094

Gnomad4 AFR exome AF: 0.780

Gnomad4 AMR exome AF: 0.900

Gnomad4 ASJ exome AF: 0.822

Gnomad4 EAS exome AF: 0.798

Gnomad4 SAS exome AF: 0.882

Gnomad4 FIN exome AF: 0.881

Gnomad4 NFE exome AF: 0.876

Gnomad4 OTH exome AF: 0.870

GnomAD4 genome AF: 0.847 AC: 128995 AN: 152228 Hom.: 54847 Cov.: 33 AF XY: 0.848 AC XY: 63095 AN XY: 74426

Gnomad4 AFR AF: 0.782

Gnomad4 AMR AF: 0.874

Gnomad4 ASJ AF: 0.830

Gnomad4 EAS AF: 0.787

Gnomad4 SAS AF: 0.875

Gnomad4 FIN AF: 0.889

Gnomad4 NFE AF: 0.878

Gnomad4 OTH AF: 0.851

Alfa AF: 0.863 Hom.: 7026

Bravo AF: 0.843

Asia WGS AF: 0.823 AC: 2864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.5
DANN	Benign	0.72

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: rs11190190; hg19: chr10-101379280;