12-104904266-T-C

Variant names:

• chr12-104904266-T-C
• rs10507187
• NM_001352171.3:c.663+5389A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001352171.3(SLC41A2):​c.663+5389A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0382 in 152,284 control chromosomes in the GnomAD database, including 155 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.038 (155 hom., cov: 32)
• Consequence: SLC41A2 NM_001352171.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC41A2	NM_001352171.3	c.663+5389A>G		intron_variant	Intron 3 of 10	ENST00000258538.8	NP_001339100.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC41A2	ENST00000258538.8	c.663+5389A>G		intron_variant	Intron 3 of 10	1	NM_001352171.3	ENSP00000258538.3
SLC41A2	ENST00000437220.1	c.229-8921A>G		intron_variant	Intron 1 of 2	5		ENSP00000391377.1

Frequencies

GnomAD3 genomes AF: 0.0382 AC: 5818 AN: 152166 Hom.: 154 Cov.: 32

Gnomad AFR AF: 0.0311

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0398

Gnomad ASJ AF: 0.0352

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0776

Gnomad FIN AF: 0.0765

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0290

Gnomad OTH AF: 0.0326

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0382 AC: 5823 AN: 152284 Hom.: 155 Cov.: 32 AF XY: 0.0415 AC XY: 3090 AN XY: 74474

African (AFR) AF: 0.0310 AC: 1290 AN: 41564

American (AMR) AF: 0.0397 AC: 608 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0352 AC: 122 AN: 3468

East Asian (EAS) AF: 0.105 AC: 545 AN: 5180

South Asian (SAS) AF: 0.0778 AC: 376 AN: 4830

European-Finnish (FIN) AF: 0.0765 AC: 811 AN: 10604

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0290 AC: 1970 AN: 68018

Other (OTH) AF: 0.0341 AC: 72 AN: 2110

Alfa AF: 0.0215 Hom.: 14

Bravo AF: 0.0344

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	13
DANN	Benign	0.82
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

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: rs10507187; hg19: chr12-105298044;