12-104866381-TACACACACACACACACACACAC-TACACACACACACACACACACACACAC

Variant names:

• chr12-104866381-T-TACAC
• rs57548373
• NM_001352171.3:c.1175+47_1175+50dupGTGT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001387131.1(SLC41A2):​c.1222_1225dupGTGT​(p.Tyr409CysfsTer12) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0053 (5 hom., cov: 0)
  • Exomes 𝑓: 0.0047 (2 hom.)
• Consequence: SLC41A2 NM_001387131.1 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 5 gene

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+47_1175+50dupGTGT		intron	N/A	NP_001339100.1	Q96JW4
	SLC41A2	NM_001387131.1		c.1222_1225dupGTGT	p.Tyr409CysfsTer12	frameshift	Exon 7 of 7	NP_001374060.1
	SLC41A2	NM_001387132.1		c.1222_1225dupGTGT	p.Tyr409CysfsTer12	frameshift	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+50_1175+51insGTGT		intron	N/A	ENSP00000258538.3	Q96JW4
	SLC41A2	ENST00000906846.1		c.1175+50_1175+51insGTGT		intron	N/A	ENSP00000576905.1
	SLC41A2	ENST00000906847.1		c.1175+50_1175+51insGTGT		intron	N/A	ENSP00000576906.1

Frequencies

GnomAD3 genomes AF: 0.00522 AC: 736 AN: 141004 Hom.: 4 Cov.: 0

Gnomad AFR AF: 0.00792

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00391

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000847

Gnomad SAS AF: 0.00473

Gnomad FIN AF: 0.000931

Gnomad MID AF: 0.00342

Gnomad NFE AF: 0.00534

Gnomad OTH AF: 0.00415

GnomAD4 exome AF: 0.00465 AC: 5977 AN: 1284760 Hom.: 2 Cov.: 0 AF XY: 0.00459 AC XY: 2898 AN XY: 631396

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00540 AC: 154 AN: 28524

American (AMR) AF: 0.00242 AC: 77 AN: 31788

Ashkenazi Jewish (ASJ) AF: 0.0000485 AC: 1 AN: 20610

East Asian (EAS) AF: 0.000585 AC: 21 AN: 35882

South Asian (SAS) AF: 0.00264 AC: 149 AN: 56348

European-Finnish (FIN) AF: 0.000660 AC: 27 AN: 40936

Middle Eastern (MID) AF: 0.00255 AC: 12 AN: 4698

European-Non Finnish (NFE) AF: 0.00526 AC: 5328 AN: 1013430

Other (OTH) AF: 0.00396 AC: 208 AN: 52544

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00527 AC: 744 AN: 141096 Hom.: 5 Cov.: 0 AF XY: 0.00516 AC XY: 354 AN XY: 68670

African (AFR) AF: 0.00812 AC: 299 AN: 36836

American (AMR) AF: 0.00391 AC: 56 AN: 14326

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3330

East Asian (EAS) AF: 0.000849 AC: 4 AN: 4710

South Asian (SAS) AF: 0.00474 AC: 20 AN: 4222

European-Finnish (FIN) AF: 0.000931 AC: 9 AN: 9666

Middle Eastern (MID) AF: 0.00370 AC: 1 AN: 270

European-Non Finnish (NFE) AF: 0.00534 AC: 347 AN: 64926

Other (OTH) AF: 0.00411 AC: 8 AN: 1946

Alfa AF: 0.00 Hom.: 405

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism

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;