NM_001352171.3:c.1708G>C

Variant names:

• chr12-104805166-C-G
• NM_001352171.3:c.1708G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001352171.3(SLC41A2):​c.1708G>C​(p.Asp570His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC41A2 NM_001352171.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.77
• Publications: 0 publications found

Genes affected

SLC41A2 (HGNC:31045): (solute carrier family 41 member 2) Predicted to enable inorganic cation transmembrane transporter activity. Predicted to be involved in magnesium ion transmembrane transport. Predicted to act upstream of or within metal ion transport. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000309266 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.746

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352171.3. 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
	SLC41A2	NM_001352171.3	MANE Select	c.1708G>C	p.Asp570His	missense	Exon 11 of 11	NP_001339100.1	Q96JW4
	SLC41A2	NM_001352169.2		c.1708G>C	p.Asp570His	missense	Exon 12 of 12	NP_001339098.1	Q96JW4
	SLC41A2	NM_001352170.3		c.1708G>C	p.Asp570His	missense	Exon 12 of 12	NP_001339099.1	Q96JW4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC41A2	ENST00000258538.8	TSL:1 MANE Select	c.1708G>C	p.Asp570His	missense	Exon 11 of 11	ENSP00000258538.3	Q96JW4
	SLC41A2	ENST00000906846.1		c.1708G>C	p.Asp570His	missense	Exon 11 of 11	ENSP00000576905.1
	SLC41A2	ENST00000906847.1		c.1708G>C	p.Asp570His	missense	Exon 11 of 11	ENSP00000576906.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.032	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		7.8
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.83
MutPred		0.27		Gain of catalytic residue at D566 (P = 0.0058)
MVP		0.36
MPC		1.5
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.72
gMVP		0.85
Mutation Taster		=52/48	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

hg19: chr12-105198944;