10-99620257-C-T

Variant names:

• chr10-99620257-C-T
• NM_031212.4:c.79G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031212.4(SLC25A28):​c.79G>A​(p.Ala27Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A27V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC25A28 NM_031212.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.15

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18287754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A28	NM_031212.4	c.79G>A	p.Ala27Thr	missense_variant	Exon 1 of 4	ENST00000370495.6	NP_112489.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A28	ENST00000370495.6	c.79G>A	p.Ala27Thr	missense_variant	Exon 1 of 4	1	NM_031212.4	ENSP00000359526.4

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1133922 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 548078

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 26

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.79G>A (p.A27T) alteration is located in exon 1 (coding exon 1) of the SLC25A28 gene. This alteration results from a G to A substitution at nucleotide position 79, causing the alanine (A) at amino acid position 27 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.087	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.50	T
M_CAP	Pathogenic	0.92	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.34	N
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.14
Sift	Benign	0.12	T
Sift4G	Benign	0.64	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.33		Loss of helix (P = 0.0167);
MVP		0.20
MPC		1.1
ClinPred		0.28	T
GERP RS		3.8
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.3
Varity_R		0.10
gMVP		0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-101380014;