12-104866381-TAC-T

Variant names:

• chr12-104866381-TAC-T
• rs57548373
• NM_001352171.3:c.1175+49_1175+50delGT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001387131.1(SLC41A2):​c.1224_1225delGT​(p.Tyr409ArgfsTer10) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0435 in 1,390,440 control chromosomes in the GnomAD database, including 67 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (57 hom., cov: 0)
  • Exomes 𝑓: 0.046 (10 hom.)
• Consequence: SLC41A2 NM_001387131.1 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.602

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 -10 ACMG points.

• BP6: Variant 12-104866381-TAC-T is Benign according to our data. Variant chr12-104866381-TAC-T is described in ClinVar as [Benign]. Clinvar id is 1258555.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC41A2	NM_001352171.3	c.1175+49_1175+50delGT		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+49_1175+50delGT		intron_variant	Intron 7 of 10	1	NM_001352171.3	ENSP00000258538.3
ENSG00000286410	ENST00000671114.1	n.71-3780_71-3779delAC		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0198 AC: 2789 AN: 140870 Hom.: 57 Cov.: 0

Gnomad AFR AF: 0.0514

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0106

Gnomad ASJ AF: 0.00240

Gnomad EAS AF: 0.00805

Gnomad SAS AF: 0.0156

Gnomad FIN AF: 0.00509

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00865

Gnomad OTH AF: 0.0156

GnomAD3 exomes AF: 0.0682 AC: 10314 AN: 151248 Hom.: 3 AF XY: 0.0696 AC XY: 5741 AN XY: 82436

Gnomad AFR exome AF: 0.0612

Gnomad AMR exome AF: 0.0582

Gnomad ASJ exome AF: 0.0417

Gnomad EAS exome AF: 0.0682

Gnomad SAS exome AF: 0.109

Gnomad FIN exome AF: 0.0642

Gnomad NFE exome AF: 0.0655

Gnomad OTH exome AF: 0.0620

GnomAD4 exome AF: 0.0462 AC: 57666 AN: 1249478 Hom.: 10 AF XY: 0.0472 AC XY: 28970 AN XY: 614338

Gnomad4 AFR exome AF: 0.0597

Gnomad4 AMR exome AF: 0.0490

Gnomad4 ASJ exome AF: 0.0300

Gnomad4 EAS exome AF: 0.0455

Gnomad4 SAS exome AF: 0.0836

Gnomad4 FIN exome AF: 0.0517

Gnomad4 NFE exome AF: 0.0437

Gnomad4 OTH exome AF: 0.0473

GnomAD4 genome AF: 0.0198 AC: 2797 AN: 140962 Hom.: 57 Cov.: 0 AF XY: 0.0190 AC XY: 1306 AN XY: 68612

Gnomad4 AFR AF: 0.0513

Gnomad4 AMR AF: 0.0106

Gnomad4 ASJ AF: 0.00240

Gnomad4 EAS AF: 0.00807

Gnomad4 SAS AF: 0.0159

Gnomad4 FIN AF: 0.00509

Gnomad4 NFE AF: 0.00865

Gnomad4 OTH AF: 0.0165

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 16, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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: rs57548373; hg19: chr12-105260159;