chr12-104866381-T-TAC

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001387131.1(SLC41A2):​c.1224_1225dupGT​(p.Tyr409CysfsTer19) 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 0.034 (85 hom., cov: 0)
  • Exomes 𝑓: 0.024 (10 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0672 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+49_1175+50dupGT		intron	N/A	NP_001339100.1	Q96JW4
	SLC41A2	NM_001387131.1		c.1224_1225dupGT	p.Tyr409CysfsTer19	frameshift	Exon 7 of 7	NP_001374060.1
	SLC41A2	NM_001387132.1		c.1224_1225dupGT	p.Tyr409CysfsTer19	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+51insGT		intron	N/A	ENSP00000258538.3	Q96JW4
	SLC41A2	ENST00000906846.1		c.1175+50_1175+51insGT		intron	N/A	ENSP00000576905.1
	SLC41A2	ENST00000906847.1		c.1175+50_1175+51insGT		intron	N/A	ENSP00000576906.1

Frequencies

GnomAD3 genomes AF: 0.0341 AC: 4808 AN: 140926 Hom.: 85 Cov.: 0

Gnomad AFR AF: 0.0462

Gnomad AMI AF: 0.00347

Gnomad AMR AF: 0.0226

Gnomad ASJ AF: 0.0551

Gnomad EAS AF: 0.0155

Gnomad SAS AF: 0.0745

Gnomad FIN AF: 0.0265

Gnomad MID AF: 0.0342

Gnomad NFE AF: 0.0292

Gnomad OTH AF: 0.0280

GnomAD2 exomes AF: 0.0219 AC: 3312 AN: 151248 AF XY: 0.0228

Gnomad AFR exome AF: 0.0334

Gnomad AMR exome AF: 0.0107

Gnomad ASJ exome AF: 0.0329

Gnomad EAS exome AF: 0.0107

Gnomad FIN exome AF: 0.0194

Gnomad NFE exome AF: 0.0199

Gnomad OTH exome AF: 0.0232

GnomAD4 exome AF: 0.0239 AC: 30508 AN: 1278850 Hom.: 10 Cov.: 0 AF XY: 0.0241 AC XY: 15160 AN XY: 628574

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

African (AFR) AF: 0.0393 AC: 1112 AN: 28318

American (AMR) AF: 0.0119 AC: 377 AN: 31734

Ashkenazi Jewish (ASJ) AF: 0.0440 AC: 901 AN: 20456

East Asian (EAS) AF: 0.0111 AC: 398 AN: 35832

South Asian (SAS) AF: 0.0446 AC: 2499 AN: 56048

European-Finnish (FIN) AF: 0.0243 AC: 990 AN: 40802

Middle Eastern (MID) AF: 0.0324 AC: 152 AN: 4692

European-Non Finnish (NFE) AF: 0.0225 AC: 22679 AN: 1008672

Other (OTH) AF: 0.0268 AC: 1400 AN: 52296

⚠️ 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: 0.0342 AC: 4821 AN: 141018 Hom.: 85 Cov.: 0 AF XY: 0.0353 AC XY: 2420 AN XY: 68620

African (AFR) AF: 0.0465 AC: 1712 AN: 36806

American (AMR) AF: 0.0225 AC: 323 AN: 14324

Ashkenazi Jewish (ASJ) AF: 0.0551 AC: 183 AN: 3324

East Asian (EAS) AF: 0.0155 AC: 73 AN: 4710

South Asian (SAS) AF: 0.0739 AC: 312 AN: 4220

European-Finnish (FIN) AF: 0.0265 AC: 256 AN: 9662

Middle Eastern (MID) AF: 0.0333 AC: 9 AN: 270

European-Non Finnish (NFE) AF: 0.0292 AC: 1896 AN: 64892

Other (OTH) AF: 0.0277 AC: 54 AN: 1946

Alfa AF: 0.0229 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;