chr12-104866499-G-A

Variant names:

• chr12-104866499-G-A
• rs2043464388
• NM_001352171.3:c.1108C>T

Variant summary

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

The NM_001352171.3(SLC41A2):​c.1108C>T​(p.His370Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000666 in 150,124 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000067 (0 hom., cov: 29)
• Consequence: SLC41A2 NM_001352171.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.33
• 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]

ENSG00000286410 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1108C>T	p.His370Tyr	missense	Exon 7 of 11	NP_001339100.1	Q96JW4
	SLC41A2	NM_001352169.2		c.1108C>T	p.His370Tyr	missense	Exon 8 of 12	NP_001339098.1	Q96JW4
	SLC41A2	NM_001352170.3		c.1108C>T	p.His370Tyr	missense	Exon 8 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.1108C>T	p.His370Tyr	missense	Exon 7 of 11	ENSP00000258538.3	Q96JW4
	SLC41A2	ENST00000906846.1		c.1108C>T	p.His370Tyr	missense	Exon 7 of 11	ENSP00000576905.1
	SLC41A2	ENST00000906847.1		c.1108C>T	p.His370Tyr	missense	Exon 7 of 11	ENSP00000576906.1

Frequencies

GnomAD3 genomes AF: 0.00000666 AC: 1 AN: 150124 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

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: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 37

GnomAD4 genome AF: 0.00000666 AC: 1 AN: 150124 Hom.: 0 Cov.: 29 AF XY: 0.0000137 AC XY: 1 AN XY: 73122

African (AFR) AF: 0.00 AC: 0 AN: 40722

American (AMR) AF: 0.00 AC: 0 AN: 14942

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5118

South Asian (SAS) AF: 0.00 AC: 0 AN: 4754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67728

Other (OTH) AF: 0.00 AC: 0 AN: 2058

ClinVar

ClinVar submissions as Germline

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	0.64
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		6.3
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.94	P
Vest4		0.73
MutPred		0.48		Gain of catalytic residue at A368 (P = 3e-04)
MVP		0.18
MPC		1.4
ClinPred		0.99	D
GERP RS		6.0
Varity_R		0.38
gMVP		0.93
Mutation Taster		=56/44	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: rs2043464388; hg19: chr12-105260277;