12-104866381-TACACACACACACACACACACAC-TACACACACACACACAC

Variant names:

• chr12-104866381-TACACAC-T
• rs57548373
• NM_001352171.3:c.1175+45_1175+50delGTGTGT

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BA1

The NM_001387131.1(SLC41A2):​c.1220_1225delGTGTGT​(p.Cys407_Val408del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.53 (19420 hom., cov: 0)
  • Exomes 𝑓: 0.42 (19362 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC41A2 NM_001387131.1 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.25
• Publications: 2 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: Benign. The variant received -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001387131.1
• BP6: Variant 12-104866381-TACACAC-T is Benign according to our data. Variant chr12-104866381-TACACAC-T is described in ClinVar as Benign. ClinVar VariationId is 1267960.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387131.1. 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.1175+45_1175+50delGTGTGT		intron	N/A	NP_001339100.1	Q96JW4
	SLC41A2	NM_001387131.1		c.1220_1225delGTGTGT	p.Cys407_Val408del	disruptive_inframe_deletion	Exon 7 of 7	NP_001374060.1
	SLC41A2	NM_001387132.1		c.1220_1225delGTGTGT	p.Cys407_Val408del	disruptive_inframe_deletion	Exon 8 of 8	NP_001374061.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC41A2	ENST00000258538.8	TSL:1 MANE Select	c.1175+45_1175+50delGTGTGT		intron	N/A	ENSP00000258538.3	Q96JW4
	SLC41A2	ENST00000906846.1		c.1175+45_1175+50delGTGTGT		intron	N/A	ENSP00000576905.1
	SLC41A2	ENST00000906847.1		c.1175+45_1175+50delGTGTGT		intron	N/A	ENSP00000576906.1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 75053 AN: 140758 Hom.: 19427 Cov.: 0

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.575

GnomAD2 exomes AF: 0.413 AC: 62517 AN: 151248 AF XY: 0.414

Gnomad AFR exome AF: 0.352

Gnomad AMR exome AF: 0.430

Gnomad ASJ exome AF: 0.474

Gnomad EAS exome AF: 0.291

Gnomad FIN exome AF: 0.433

Gnomad NFE exome AF: 0.444

Gnomad OTH exome AF: 0.437

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.419 AC: 537454 AN: 1281648 Hom.: 19362 AF XY: 0.418 AC XY: 263224 AN XY: 629744

African (AFR) AF: 0.325 AC: 9228 AN: 28372

American (AMR) AF: 0.408 AC: 12875 AN: 31568

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 9224 AN: 20516

East Asian (EAS) AF: 0.317 AC: 11239 AN: 35510

South Asian (SAS) AF: 0.340 AC: 19088 AN: 56078

European-Finnish (FIN) AF: 0.403 AC: 16427 AN: 40760

Middle Eastern (MID) AF: 0.457 AC: 2148 AN: 4698

European-Non Finnish (NFE) AF: 0.430 AC: 435404 AN: 1011748

Other (OTH) AF: 0.416 AC: 21821 AN: 52398

GnomAD4 genome AF: 0.533 AC: 75073 AN: 140848 Hom.: 19420 Cov.: 0 AF XY: 0.528 AC XY: 36144 AN XY: 68516

African (AFR) AF: 0.429 AC: 15758 AN: 36730

American (AMR) AF: 0.566 AC: 8083 AN: 14284

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2150 AN: 3324

East Asian (EAS) AF: 0.346 AC: 1627 AN: 4706

South Asian (SAS) AF: 0.427 AC: 1797 AN: 4212

European-Finnish (FIN) AF: 0.507 AC: 4899 AN: 9656

Middle Eastern (MID) AF: 0.637 AC: 172 AN: 270

European-Non Finnish (NFE) AF: 0.601 AC: 38975 AN: 64856

Other (OTH) AF: 0.571 AC: 1112 AN: 1946

Alfa AF: 0.354 Hom.: 405

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs57548373; hg19: chr12-105260159;