chr10-99620295-C-A

Variant names:

• chr10-99620295-C-A
• rs2034757962
• NM_031212.4:c.41G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031212.4(SLC25A28):​c.41G>T​(p.Gly14Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000039 in 1,025,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G14E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 0.0000039 (0 hom.)
• Consequence: SLC25A28 NM_031212.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19933665).

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.41G>T	p.Gly14Val	missense	Exon 1 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.41G>T	p.Gly14Val	missense	Exon 1 of 4	ENSP00000359526.4	Q96A46-1
	SLC25A28	ENST00000913498.1		c.41G>T	p.Gly14Val	missense	Exon 1 of 4	ENSP00000583557.1
	SLC25A28	ENST00000966520.1		c.41G>T	p.Gly14Val	missense	Exon 1 of 3	ENSP00000636579.1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 0.00000390 AC: 4 AN: 1025530 Hom.: 0 Cov.: 26 AF XY: 0.00000616 AC XY: 3 AN XY: 487014

African (AFR) AF: 0.00 AC: 0 AN: 20674

American (AMR) AF: 0.00 AC: 0 AN: 7250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11790

East Asian (EAS) AF: 0.00 AC: 0 AN: 20838

South Asian (SAS) AF: 0.00 AC: 0 AN: 20038

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18902

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2648

European-Non Finnish (NFE) AF: 0.00000453 AC: 4 AN: 883920

Other (OTH) AF: 0.00 AC: 0 AN: 39470

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.085	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.53	T
M_CAP	Pathogenic	0.97	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.2
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.020	D
Polyphen		0.0040	B
Vest4		0.20
MutPred		0.39		Gain of sheet (P = 0.0166)
MVP		0.093
MPC		1.4
ClinPred		0.53	D
GERP RS		4.0
PromoterAI		-0.077	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		4.0
Varity_R		0.29
gMVP		0.61
Mutation Taster		=87/13	polymorphism

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

dbSNP: rs2034757962; hg19: chr10-101380052;