NM_001352171.3:c.1456A>G

Variant names:

• chr12-104844552-T-C
• rs1170376633
• NM_001352171.3:c.1456A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001352171.3(SLC41A2):​c.1456A>G​(p.Thr486Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000703 in 1,422,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SLC41A2 NM_001352171.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.62
• 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]

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=0.19441095).

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.1456A>G	p.Thr486Ala	missense	Exon 10 of 11	NP_001339100.1	Q96JW4
	SLC41A2	NM_001352169.2		c.1456A>G	p.Thr486Ala	missense	Exon 11 of 12	NP_001339098.1	Q96JW4
	SLC41A2	NM_001352170.3		c.1456A>G	p.Thr486Ala	missense	Exon 11 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.1456A>G	p.Thr486Ala	missense	Exon 10 of 11	ENSP00000258538.3	Q96JW4
	SLC41A2	ENST00000906846.1		c.1456A>G	p.Thr486Ala	missense	Exon 10 of 11	ENSP00000576905.1
	SLC41A2	ENST00000906847.1		c.1456A>G	p.Thr486Ala	missense	Exon 10 of 11	ENSP00000576906.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1422520 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 706860

African (AFR) AF: 0.00 AC: 0 AN: 32112

American (AMR) AF: 0.00 AC: 0 AN: 40030

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25512

East Asian (EAS) AF: 0.00 AC: 0 AN: 38058

South Asian (SAS) AF: 0.00 AC: 0 AN: 77904

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52712

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5658

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1091692

Other (OTH) AF: 0.0000170 AC: 1 AN: 58842

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	0.10
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.068
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		5.6
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.20
Sift	Benign	0.19	T
Sift4G	Benign	0.23	T
Polyphen		0.051	B
Vest4		0.30
MutPred		0.47		Gain of catalytic residue at T486 (P = 0)
MVP		0.082
MPC		0.56
ClinPred		0.92	D
GERP RS		5.6
Varity_R		0.34
gMVP		0.65
Mutation Taster		=61/39	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: rs1170376633; hg19: chr12-105238330;