10-99620226-A-G

Variant names:

• chr10-99620226-A-G
• rs1377538215
• NM_031212.4:c.110T>C

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.110T>C​(p.Val37Ala) 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. 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. V37G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 0)
• Consequence: SLC25A28 NM_031212.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• 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=0.17357513).

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.110T>C	p.Val37Ala	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.110T>C	p.Val37Ala	missense	Exon 1 of 4	ENSP00000359526.4	Q96A46-1
	SLC25A28	ENST00000913498.1		c.110T>C	p.Val37Ala	missense	Exon 1 of 4	ENSP00000583557.1
	SLC25A28	ENST00000966520.1		c.110T>C	p.Val37Ala	missense	Exon 1 of 3	ENSP00000636579.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.090	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.41	T
M_CAP	Pathogenic	0.98	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.1
PrimateAI	Pathogenic	0.97	D
PROVEAN	Benign	0.19	N
REVEL	Benign	0.14
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.33	T
Polyphen		0.0010	B
Vest4		0.13
MutPred		0.44		Loss of stability (P = 0.098)
MVP		0.082
MPC		1.4
ClinPred		0.24	T
GERP RS		2.6
PromoterAI		0.041	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.9
Varity_R		0.058
gMVP		0.31
Mutation Taster		=93/7	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: rs1377538215; hg19: chr10-101379983;