chr12-104805175-G-C

Variant names:

• chr12-104805175-G-C
• rs540046926
• NM_001352171.3:c.1699C>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.1699C>G​(p.Arg567Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,610,816 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R567L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SLC41A2 NM_001352171.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.12
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1768901).

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.1699C>G	p.Arg567Gly	missense	Exon 11 of 11	NP_001339100.1	Q96JW4
	SLC41A2	NM_001352169.2		c.1699C>G	p.Arg567Gly	missense	Exon 12 of 12	NP_001339098.1	Q96JW4
	SLC41A2	NM_001352170.3		c.1699C>G	p.Arg567Gly	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.1699C>G	p.Arg567Gly	missense	Exon 11 of 11	ENSP00000258538.3	Q96JW4
	SLC41A2	ENST00000906846.1		c.1699C>G	p.Arg567Gly	missense	Exon 11 of 11	ENSP00000576905.1
	SLC41A2	ENST00000906847.1		c.1699C>G	p.Arg567Gly	missense	Exon 11 of 11	ENSP00000576906.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152112 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000403 AC: 1 AN: 248086 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000296

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1458586 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 725542

African (AFR) AF: 0.00 AC: 0 AN: 33260

American (AMR) AF: 0.00 AC: 0 AN: 44260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26028

East Asian (EAS) AF: 0.00 AC: 0 AN: 39574

South Asian (SAS) AF: 0.00 AC: 0 AN: 85704

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1110482

Other (OTH) AF: 0.00 AC: 0 AN: 60236

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152230 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74408

African (AFR) AF: 0.00 AC: 0 AN: 41540

American (AMR) AF: 0.0000655 AC: 1 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2114

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	Benign	0.16
BayesDel_addAF	Benign	0.0057	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		4.1
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.13
Sift	Benign	0.15	T
Sift4G	Benign	0.27	T
Polyphen		0.83	P
Vest4		0.43
MutPred		0.39		Gain of catalytic residue at G569 (P = 0.0062)
MVP		0.068
MPC		1.2
ClinPred		0.98	D
GERP RS		3.7
Varity_R		0.28
gMVP		0.54
Mutation Taster		=73/27	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: rs540046926; hg19: chr12-105198953;