NM_031212.4:c.908G>A

Variant names:

• chr10-99611036-C-T
• NM_031212.4:c.908G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_031212.4(SLC25A28):​c.908G>A​(p.Gly303Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC25A28 NM_031212.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.90
• Publications: 0 publications found

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]

ENSG00000229278 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031212.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A28	NM_031212.4	MANE Select	c.908G>A	p.Gly303Glu	missense	Exon 4 of 4	NP_112489.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A28	ENST00000370495.6	TSL:1 MANE Select	c.908G>A	p.Gly303Glu	missense	Exon 4 of 4	ENSP00000359526.4	Q96A46-1
	SLC25A28	ENST00000913498.1		c.926G>A	p.Gly309Glu	missense	Exon 4 of 4	ENSP00000583557.1
	SLC25A28	ENST00000966520.1		c.851G>A	p.Gly284Glu	missense	Exon 3 of 3	ENSP00000636579.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.089	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.9
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.62
Sift	Benign	0.43	T
Sift4G	Benign	0.35	T
Polyphen		0.76	P
Vest4		0.38
MutPred		0.45		Gain of disorder (P = 0.1297)
MVP		0.44
MPC		2.6
ClinPred		0.96	D
GERP RS		5.0
Varity_R		0.40
gMVP		0.87
Mutation Taster		=43/57	disease causing

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

Other links and lift over

hg19: chr10-101370793;