10-99610980-T-A

Variant names:

• chr10-99610980-T-A
• rs1004763338
• NM_031212.4:c.964A>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.964A>T​(p.Thr322Ser) 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. 16/22 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. T322A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC25A28 NM_031212.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61
• 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=0.099856764).

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.964A>T	p.Thr322Ser	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.964A>T	p.Thr322Ser	missense	Exon 4 of 4	ENSP00000359526.4	Q96A46-1
	SLC25A28	ENST00000913498.1		c.982A>T	p.Thr328Ser	missense	Exon 4 of 4	ENSP00000583557.1
	SLC25A28	ENST00000966520.1		c.907A>T	p.Thr303Ser	missense	Exon 3 of 3	ENSP00000636579.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Benign	0.85
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.53	N
PhyloP100		1.6
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	0.14	N
REVEL	Benign	0.21
Sift	Benign	0.75	T
Sift4G	Benign	0.48	T
Polyphen		0.0040	B
Vest4		0.10
MutPred		0.31		Gain of MoRF binding (P = 0.1103)
MVP		0.24
MPC		1.1
ClinPred		0.30	T
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.034
gMVP		0.64
Mutation Taster		=90/10	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: rs1004763338; hg19: chr10-101370737;