12-104886153-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001352171.3(SLC41A2):c.1027+140G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 821,810 control chromosomes in the GnomAD database, including 95,350 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (16130 hom., cov: 32)
  • Exomes 𝑓: 0.48 (79220 hom.)
• Consequence: SLC41A2 NM_001352171.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.260

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 12-104886153-C-A is Benign according to our data. Variant chr12-104886153-C-A is described in ClinVar as [Benign]. Clinvar id is 1289782.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC41A2	NM_001352171.3	c.1027+140G>T		intron_variant		ENST00000258538.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC41A2	ENST00000258538.8	c.1027+140G>T		intron_variant		1	NM_001352171.3	P1

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68819 AN: 151668 Hom.: 16126 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.497

GnomAD4 exome AF: 0.480 AC: 321745 AN: 670022 Hom.: 79220 AF XY: 0.476 AC XY: 160703 AN XY: 337320

Gnomad4 AFR exome AF: 0.359

Gnomad4 AMR exome AF: 0.496

Gnomad4 ASJ exome AF: 0.583

Gnomad4 EAS exome AF: 0.235

Gnomad4 SAS exome AF: 0.322

Gnomad4 FIN exome AF: 0.455

Gnomad4 NFE exome AF: 0.510

Gnomad4 OTH exome AF: 0.481

GnomAD4 genome AF: 0.454 AC: 68844 AN: 151788 Hom.: 16130 Cov.: 32 AF XY: 0.450 AC XY: 33405 AN XY: 74182

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.509

Gnomad4 OTH AF: 0.494

Bravo AF: 0.458

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.9
Dann	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs17829927; hg19: chr12-105279931;