NM_031212.4:c.110T>G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_031212.4(SLC25A28):​c.110T>G​(p.Val37Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 0)
  • 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: 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1894725).

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>G	p.Val37Gly	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>G	p.Val37Gly	missense	Exon 1 of 4	ENSP00000359526.4	Q96A46-1
	SLC25A28	ENST00000913498.1		c.110T>G	p.Val37Gly	missense	Exon 1 of 4	ENSP00000583557.1
	SLC25A28	ENST00000966520.1		c.110T>G	p.Val37Gly	missense	Exon 1 of 3	ENSP00000636579.1

Frequencies

GnomAD3 genomes AF: 0.000133 AC: 4 AN: 30046 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000436

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000673

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1082532 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 529854

African (AFR) AF: 0.00 AC: 0 AN: 21950

American (AMR) AF: 0.00 AC: 0 AN: 16040

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16554

East Asian (EAS) AF: 0.00 AC: 0 AN: 26194

South Asian (SAS) AF: 0.00 AC: 0 AN: 57938

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3066

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 871176

Other (OTH) AF: 0.00 AC: 0 AN: 44072

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000133 AC: 4 AN: 30072 Hom.: 0 Cov.: 0 AF XY: 0.000132 AC XY: 2 AN XY: 15132

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000434 AC: 3 AN: 6908

American (AMR) AF: 0.00 AC: 0 AN: 2398

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 716

East Asian (EAS) AF: 0.00 AC: 0 AN: 1386

South Asian (SAS) AF: 0.00 AC: 0 AN: 950

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2146

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 60

European-Non Finnish (NFE) AF: 0.0000673 AC: 1 AN: 14864

Other (OTH) AF: 0.00 AC: 0 AN: 410

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00241 Hom.: 0

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	Benign	0.041
BayesDel_addAF	Benign	-0.0020	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Benign	0.93
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.31	T
M_CAP	Pathogenic	0.99	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.1
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	0.14	N
REVEL	Benign	0.24
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.019	D
Polyphen		0.0040	B
Vest4		0.20
MutPred		0.39		Gain of relative solvent accessibility (P = 0.0082)
MVP		0.12
MPC		1.5
ClinPred		0.35	T
GERP RS		2.6
PromoterAI		-0.0027	Neutral
Varity_R		0.12
gMVP		0.45
Mutation Taster		=88/12	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;