chr12-104805069-G-A

Variant names:

• chr12-104805069-G-A
• rs12298260
• NM_001352171.3:c.*83C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001352171.3(SLC41A2):​c.*83C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00427 in 1,225,156 control chromosomes in the GnomAD database, including 160 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (92 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (68 hom.)
• Consequence: SLC41A2 NM_001352171.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.71
• 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]

ENSG00000309266 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 12-104805069-G-A is Benign according to our data. Variant chr12-104805069-G-A is described in ClinVar as Benign. ClinVar VariationId is 1290289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0666 is higher than 0.05.

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.*83C>T		3_prime_UTR	Exon 11 of 11	NP_001339100.1	Q96JW4
	SLC41A2	NM_001352169.2		c.*83C>T		3_prime_UTR	Exon 12 of 12	NP_001339098.1	Q96JW4
	SLC41A2	NM_001352170.3		c.*83C>T		3_prime_UTR	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.*83C>T		3_prime_UTR	Exon 11 of 11	ENSP00000258538.3	Q96JW4
	SLC41A2	ENST00000906846.1		c.*83C>T		3_prime_UTR	Exon 11 of 11	ENSP00000576905.1
	SLC41A2	ENST00000906847.1		c.*83C>T		3_prime_UTR	Exon 11 of 11	ENSP00000576906.1

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 2993 AN: 152100 Hom.: 92 Cov.: 32

Gnomad AFR AF: 0.0685

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00721

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: 0.000397

Gnomad OTH AF: 0.00955

GnomAD4 exome AF: 0.00207 AC: 2217 AN: 1072938 Hom.: 68 Cov.: 13 AF XY: 0.00182 AC XY: 970 AN XY: 533350

African (AFR) AF: 0.0720 AC: 1698 AN: 23578

American (AMR) AF: 0.00470 AC: 122 AN: 25930

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17354

East Asian (EAS) AF: 0.00 AC: 0 AN: 34812

South Asian (SAS) AF: 0.000153 AC: 8 AN: 52450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44444

Middle Eastern (MID) AF: 0.00320 AC: 10 AN: 3122

European-Non Finnish (NFE) AF: 0.000182 AC: 150 AN: 825446

Other (OTH) AF: 0.00500 AC: 229 AN: 45802

GnomAD4 genome AF: 0.0198 AC: 3010 AN: 152218 Hom.: 92 Cov.: 32 AF XY: 0.0185 AC XY: 1375 AN XY: 74426

African (AFR) AF: 0.0687 AC: 2853 AN: 41512

American (AMR) AF: 0.00720 AC: 110 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

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

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68012

Other (OTH) AF: 0.00945 AC: 20 AN: 2116

Alfa AF: 0.00698 Hom.: 35

Bravo AF: 0.0220

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.55
PhyloP100		1.7
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: rs12298260; hg19: chr12-105198847;