12-104866381-TACACAC-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC41A2	NM_001352171.3	c.1175+45_1175+50delGTGTGT		intron_variant	Intron 7 of 10	ENST00000258538.8	NP_001339100.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC41A2	ENST00000258538.8	c.1175+45_1175+50delGTGTGT		intron_variant	Intron 7 of 10	1	NM_001352171.3	ENSP00000258538.3
ENSG00000286410	ENST00000671114.1	n.71-3780_71-3775delACACAC		intron_variant	Intron 1 of 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

GnomAD3 exomes AF: 0.413 AC: 62517 AN: 151248 Hom.: 4160 AF XY: 0.414 AC XY: 34088 AN XY: 82436

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 SAS exome AF: 0.352

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

Gnomad4 AFR exome AF: 0.325

Gnomad4 AMR exome AF: 0.408

Gnomad4 ASJ exome AF: 0.450

Gnomad4 EAS exome AF: 0.317

Gnomad4 SAS exome AF: 0.340

Gnomad4 FIN exome AF: 0.403

Gnomad4 NFE exome AF: 0.430

Gnomad4 OTH exome AF: 0.416

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

Gnomad4 AFR AF: 0.429

Gnomad4 AMR AF: 0.566

Gnomad4 ASJ AF: 0.647

Gnomad4 EAS AF: 0.346

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.601

Gnomad4 OTH AF: 0.571

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs57548373; hg19: chr12-105260159;