10-99612654-T-C

Position:

• chr10-99612654-T-C

Variant summary

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

The NM_031212.4(SLC25A28):​c.521-55A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 1,607,234 control chromosomes in the GnomAD database, including 608,909 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 (54808 hom., cov: 30)
  • Exomes 𝑓: 0.87 (554101 hom.)
• Consequence: SLC25A28 NM_031212.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.398

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=-0.85).
• 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.521-55A>G		intron_variant		ENST00000370495.6	NP_112489.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A28	ENST00000370495.6	c.521-55A>G		intron_variant		1	NM_031212.4	ENSP00000359526.4

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128785 AN: 151938 Hom.: 54766 Cov.: 30

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.830

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.874

Gnomad FIN AF: 0.889

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.878

Gnomad OTH AF: 0.856

GnomAD3 exomes AF: 0.866 AC: 215238 AN: 248402 Hom.: 93437 AF XY: 0.870 AC XY: 117198 AN XY: 134776

Gnomad AFR exome AF: 0.781

Gnomad AMR exome AF: 0.901

Gnomad ASJ exome AF: 0.837

Gnomad EAS exome AF: 0.778

Gnomad SAS exome AF: 0.879

Gnomad FIN exome AF: 0.889

Gnomad NFE exome AF: 0.877

Gnomad OTH exome AF: 0.873

GnomAD4 exome AF: 0.872 AC: 1269072 AN: 1455178 Hom.: 554101 Cov.: 29 AF XY: 0.873 AC XY: 632344 AN XY: 724448

Gnomad4 AFR exome AF: 0.781

Gnomad4 AMR exome AF: 0.899

Gnomad4 ASJ exome AF: 0.834

Gnomad4 EAS exome AF: 0.790

Gnomad4 SAS exome AF: 0.882

Gnomad4 FIN exome AF: 0.888

Gnomad4 NFE exome AF: 0.876

Gnomad4 OTH exome AF: 0.865

GnomAD4 genome AF: 0.848 AC: 128884 AN: 152056 Hom.: 54808 Cov.: 30 AF XY: 0.848 AC XY: 63033 AN XY: 74314

Gnomad4 AFR AF: 0.783

Gnomad4 AMR AF: 0.874

Gnomad4 ASJ AF: 0.830

Gnomad4 EAS AF: 0.787

Gnomad4 SAS AF: 0.874

Gnomad4 FIN AF: 0.889

Gnomad4 NFE AF: 0.878

Gnomad4 OTH AF: 0.855

Alfa AF: 0.871 Hom.: 122030

Bravo AF: 0.843

Asia WGS AF: 0.823 AC: 2866 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	4.1
DANN	Benign	0.52
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: rs880568; hg19: chr10-101372411; COSMIC: COSV65125804; COSMIC: COSV65125804;