12-104866381-TACACACAC-T

Variant names:

• chr12-104866381-TACACACAC-T
• rs57548373
• NM_001352171.3:c.1175+43_1175+50delGTGTGTGT

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001387131.1(SLC41A2):​c.1218_1225delGTGTGTGT​(p.Cys407ArgfsTer10) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,112,090 control chromosomes in the GnomAD database, including 97 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (107 hom., cov: 0)
  • Exomes 𝑓: 0.11 (97 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC41A2 NM_001387131.1 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 12-104866381-TACACACAC-T is Benign according to our data. Variant chr12-104866381-TACACACAC-T is described in ClinVar as Benign. ClinVar VariationId is 1259817.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 97 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+43_1175+50delGTGTGTGT		intron	N/A	NP_001339100.1	Q96JW4
	SLC41A2	NM_001387131.1		c.1218_1225delGTGTGTGT	p.Cys407ArgfsTer10	frameshift	Exon 7 of 7	NP_001374060.1
	SLC41A2	NM_001387132.1		c.1218_1225delGTGTGTGT	p.Cys407ArgfsTer10	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+43_1175+50delGTGTGTGT		intron	N/A	ENSP00000258538.3	Q96JW4
	SLC41A2	ENST00000906846.1		c.1175+43_1175+50delGTGTGTGT		intron	N/A	ENSP00000576905.1
	SLC41A2	ENST00000906847.1		c.1175+43_1175+50delGTGTGTGT		intron	N/A	ENSP00000576906.1

Frequencies

GnomAD3 genomes AF: 0.0289 AC: 4064 AN: 140624 Hom.: 106 Cov.: 0

Gnomad AFR AF: 0.0503

Gnomad AMI AF: 0.0116

Gnomad AMR AF: 0.0260

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.0156

Gnomad FIN AF: 0.00952

Gnomad MID AF: 0.0483

Gnomad NFE AF: 0.0123

Gnomad OTH AF: 0.0353

GnomAD2 exomes AF: 0.155 AC: 23397 AN: 151248 AF XY: 0.156

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.166

Gnomad ASJ exome AF: 0.186

Gnomad EAS exome AF: 0.201

Gnomad FIN exome AF: 0.121

Gnomad NFE exome AF: 0.163

Gnomad OTH exome AF: 0.155

GnomAD4 exome AF: 0.106 AC: 118319 AN: 1112090 Hom.: 97 AF XY: 0.108 AC XY: 59119 AN XY: 548570

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

African (AFR) AF: 0.0977 AC: 2638 AN: 26988

American (AMR) AF: 0.161 AC: 4874 AN: 30212

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 2875 AN: 18212

East Asian (EAS) AF: 0.188 AC: 6471 AN: 34382

South Asian (SAS) AF: 0.0773 AC: 4177 AN: 54046

European-Finnish (FIN) AF: 0.103 AC: 3909 AN: 38116

Middle Eastern (MID) AF: 0.122 AC: 510 AN: 4180

European-Non Finnish (NFE) AF: 0.102 AC: 87585 AN: 859556

Other (OTH) AF: 0.114 AC: 5280 AN: 46398

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.0289 AC: 4069 AN: 140712 Hom.: 107 Cov.: 0 AF XY: 0.0296 AC XY: 2024 AN XY: 68444

African (AFR) AF: 0.0503 AC: 1851 AN: 36810

American (AMR) AF: 0.0259 AC: 370 AN: 14284

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 62 AN: 3316

East Asian (EAS) AF: 0.156 AC: 735 AN: 4702

South Asian (SAS) AF: 0.0159 AC: 67 AN: 4216

European-Finnish (FIN) AF: 0.00952 AC: 91 AN: 9562

Middle Eastern (MID) AF: 0.0485 AC: 13 AN: 268

European-Non Finnish (NFE) AF: 0.0123 AC: 798 AN: 64750

Other (OTH) AF: 0.0371 AC: 72 AN: 1940

Alfa AF: 0.118 Hom.: 405

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

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;