12-104866381-TACACACACACACACACACACAC-TACACACACACACACACAC

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001387131.1(SLC41A2):​c.1222_1225delGTGT​(p.Val408ThrfsTer18) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0204 in 1,414,436 control chromosomes in the GnomAD database, including 97 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (56 hom., cov: 0)
  • Exomes 𝑓: 0.020 (41 hom.)
• Consequence: SLC41A2 NM_001387131.1 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.25
• 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 -10 ACMG points.

• BP6: Variant 12-104866381-TACAC-T is Benign according to our data. Variant chr12-104866381-TACAC-T is described in ClinVar as Benign. ClinVar VariationId is 1179931.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.115 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+47_1175+50delGTGT		intron	N/A	NP_001339100.1	Q96JW4
	SLC41A2	NM_001387131.1		c.1222_1225delGTGT	p.Val408ThrfsTer18	frameshift	Exon 7 of 7	NP_001374060.1
	SLC41A2	NM_001387132.1		c.1222_1225delGTGT	p.Val408ThrfsTer18	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+47_1175+50delGTGT		intron	N/A	ENSP00000258538.3	Q96JW4
	SLC41A2	ENST00000906846.1		c.1175+47_1175+50delGTGT		intron	N/A	ENSP00000576905.1
	SLC41A2	ENST00000906847.1		c.1175+47_1175+50delGTGT		intron	N/A	ENSP00000576906.1

Frequencies

GnomAD3 genomes AF: 0.0243 AC: 3428 AN: 140950 Hom.: 54 Cov.: 0

Gnomad AFR AF: 0.0248

Gnomad AMI AF: 0.00694

Gnomad AMR AF: 0.0338

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.0360

Gnomad FIN AF: 0.0280

Gnomad MID AF: 0.0240

Gnomad NFE AF: 0.0142

Gnomad OTH AF: 0.0228

GnomAD2 exomes AF: 0.0336 AC: 5080 AN: 151248 AF XY: 0.0315

Gnomad AFR exome AF: 0.0322

Gnomad AMR exome AF: 0.0558

Gnomad ASJ exome AF: 0.0135

Gnomad EAS exome AF: 0.105

Gnomad FIN exome AF: 0.0284

Gnomad NFE exome AF: 0.0186

Gnomad OTH exome AF: 0.0246

GnomAD4 exome AF: 0.0199 AC: 25403 AN: 1273394 Hom.: 41 AF XY: 0.0201 AC XY: 12609 AN XY: 625838

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

African (AFR) AF: 0.0255 AC: 725 AN: 28406

American (AMR) AF: 0.0486 AC: 1531 AN: 31532

Ashkenazi Jewish (ASJ) AF: 0.0140 AC: 286 AN: 20480

East Asian (EAS) AF: 0.127 AC: 4502 AN: 35474

South Asian (SAS) AF: 0.0321 AC: 1792 AN: 55830

European-Finnish (FIN) AF: 0.0251 AC: 1020 AN: 40622

Middle Eastern (MID) AF: 0.0236 AC: 110 AN: 4668

European-Non Finnish (NFE) AF: 0.0142 AC: 14219 AN: 1004286

Other (OTH) AF: 0.0234 AC: 1218 AN: 52096

⚠️ 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: 0.0244 AC: 3443 AN: 141042 Hom.: 56 Cov.: 0 AF XY: 0.0255 AC XY: 1750 AN XY: 68642

African (AFR) AF: 0.0248 AC: 913 AN: 36824

American (AMR) AF: 0.0343 AC: 491 AN: 14326

Ashkenazi Jewish (ASJ) AF: 0.0159 AC: 53 AN: 3328

East Asian (EAS) AF: 0.123 AC: 580 AN: 4706

South Asian (SAS) AF: 0.0358 AC: 151 AN: 4220

European-Finnish (FIN) AF: 0.0280 AC: 270 AN: 9658

Middle Eastern (MID) AF: 0.0259 AC: 7 AN: 270

European-Non Finnish (NFE) AF: 0.0142 AC: 923 AN: 64904

Other (OTH) AF: 0.0252 AC: 49 AN: 1942

Alfa AF: 0.0202 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		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs57548373; hg19: chr12-105260159;