chr12-104866381-TACACACACAC-T

Variant names:

• chr12-104866381-TACACACACAC-T
• rs57548373
• NM_001352171.3:c.1175+41_1175+50delGTGTGTGTGT

Variant summary

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

The NM_001387131.1(SLC41A2):​c.1216_1225delGTGTGTGTGT​(p.Val406ThrfsTer18) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00643 in 1,419,900 control chromosomes in the GnomAD database, including 71 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.018 (56 hom., cov: 0)
  • Exomes 𝑓: 0.0052 (15 hom.)
• Consequence: SLC41A2 NM_001387131.1 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94
• 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 (AFR) allele frequency at 95% confidence interval = 0.0549 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+41_1175+50delGTGTGTGTGT		intron	N/A	NP_001339100.1	Q96JW4
	SLC41A2	NM_001387131.1		c.1216_1225delGTGTGTGTGT	p.Val406ThrfsTer18	frameshift	Exon 7 of 7	NP_001374060.1
	SLC41A2	NM_001387132.1		c.1216_1225delGTGTGTGTGT	p.Val406ThrfsTer18	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+41_1175+50delGTGTGTGTGT		intron	N/A	ENSP00000258538.3	Q96JW4
	SLC41A2	ENST00000906846.1		c.1175+41_1175+50delGTGTGTGTGT		intron	N/A	ENSP00000576905.1
	SLC41A2	ENST00000906847.1		c.1175+41_1175+50delGTGTGTGTGT		intron	N/A	ENSP00000576906.1

Frequencies

GnomAD3 genomes AF: 0.0179 AC: 2520 AN: 140992 Hom.: 56 Cov.: 0

Gnomad AFR AF: 0.0570

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.000601

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00284

Gnomad FIN AF: 0.00197

Gnomad MID AF: 0.00342

Gnomad NFE AF: 0.00283

Gnomad OTH AF: 0.0181

GnomAD2 exomes AF: 0.0132 AC: 1992 AN: 151248 AF XY: 0.0119

Gnomad AFR exome AF: 0.0681

Gnomad AMR exome AF: 0.0135

Gnomad ASJ exome AF: 0.00691

Gnomad EAS exome AF: 0.0197

Gnomad FIN exome AF: 0.00516

Gnomad NFE exome AF: 0.00719

Gnomad OTH exome AF: 0.00963

GnomAD4 exome AF: 0.00516 AC: 6604 AN: 1278816 Hom.: 15 AF XY: 0.00515 AC XY: 3236 AN XY: 628368

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

African (AFR) AF: 0.0556 AC: 1582 AN: 28448

American (AMR) AF: 0.0121 AC: 381 AN: 31506

Ashkenazi Jewish (ASJ) AF: 0.00465 AC: 95 AN: 20424

East Asian (EAS) AF: 0.0105 AC: 372 AN: 35478

South Asian (SAS) AF: 0.00558 AC: 313 AN: 56112

European-Finnish (FIN) AF: 0.00399 AC: 162 AN: 40628

Middle Eastern (MID) AF: 0.0127 AC: 59 AN: 4662

European-Non Finnish (NFE) AF: 0.00321 AC: 3243 AN: 1009298

Other (OTH) AF: 0.00760 AC: 397 AN: 52260

⚠️ 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: 0.0179 AC: 2525 AN: 141084 Hom.: 56 Cov.: 0 AF XY: 0.0175 AC XY: 1203 AN XY: 68658

African (AFR) AF: 0.0570 AC: 2098 AN: 36832

American (AMR) AF: 0.0121 AC: 174 AN: 14322

Ashkenazi Jewish (ASJ) AF: 0.000601 AC: 2 AN: 3330

East Asian (EAS) AF: 0.00 AC: 0 AN: 4710

South Asian (SAS) AF: 0.00284 AC: 12 AN: 4220

European-Finnish (FIN) AF: 0.00197 AC: 19 AN: 9662

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

European-Non Finnish (NFE) AF: 0.00283 AC: 184 AN: 64928

Other (OTH) AF: 0.0180 AC: 35 AN: 1946

Alfa AF: 0.0121 Hom.: 405

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9
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;