NM_001352171.3:c.1175+15_1175+16delAT

Variant names:

• chr12-104866415-CAT-C
• rs757344904
• NM_001352171.3:c.1175+15_1175+16delAT

Variant summary

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

The NM_001352171.3(SLC41A2):​c.1175+15_1175+16delAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00573 in 1,530,446 control chromosomes in the GnomAD database, including 250 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (231 hom., cov: 28)
  • Exomes 𝑓: 0.0029 (19 hom.)
• Consequence: SLC41A2 NM_001352171.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.02
• Publications: 0 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 12-104866415-CAT-C is Benign according to our data. Variant chr12-104866415-CAT-C is described in ClinVar as Benign. ClinVar VariationId is 1228445.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352171.3. 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+15_1175+16delAT		intron	N/A	NP_001339100.1	Q96JW4
	SLC41A2	NM_001387131.1		c.1190_1191delAT	p.Tyr397CysfsTer22	frameshift	Exon 7 of 7	NP_001374060.1
	SLC41A2	NM_001387132.1		c.1190_1191delAT	p.Tyr397CysfsTer22	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+15_1175+16delAT		intron	N/A	ENSP00000258538.3	Q96JW4
	SLC41A2	ENST00000906846.1		c.1175+15_1175+16delAT		intron	N/A	ENSP00000576905.1
	SLC41A2	ENST00000906847.1		c.1175+15_1175+16delAT		intron	N/A	ENSP00000576906.1

Frequencies

GnomAD3 genomes AF: 0.0348 AC: 4766 AN: 136944 Hom.: 232 Cov.: 28

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000223

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0105

Gnomad NFE AF: 0.000612

Gnomad OTH AF: 0.0231

GnomAD2 exomes AF: 0.00793 AC: 1594 AN: 200884 AF XY: 0.00589

Gnomad AFR exome AF: 0.0835

Gnomad AMR exome AF: 0.00633

Gnomad ASJ exome AF: 0.00417

Gnomad EAS exome AF: 0.0000633

Gnomad FIN exome AF: 0.00261

Gnomad NFE exome AF: 0.00203

Gnomad OTH exome AF: 0.00577

GnomAD4 exome AF: 0.00286 AC: 3991 AN: 1393396 Hom.: 19 AF XY: 0.00253 AC XY: 1748 AN XY: 692274

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

African (AFR) AF: 0.0934 AC: 2513 AN: 26918

American (AMR) AF: 0.00726 AC: 258 AN: 35558

Ashkenazi Jewish (ASJ) AF: 0.00194 AC: 45 AN: 23146

East Asian (EAS) AF: 0.0000526 AC: 2 AN: 38046

South Asian (SAS) AF: 0.00127 AC: 101 AN: 79328

European-Finnish (FIN) AF: 0.00146 AC: 71 AN: 48612

Middle Eastern (MID) AF: 0.00579 AC: 30 AN: 5184

European-Non Finnish (NFE) AF: 0.000570 AC: 615 AN: 1079818

Other (OTH) AF: 0.00627 AC: 356 AN: 56786

⚠️ 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: 0.0349 AC: 4780 AN: 137050 Hom.: 231 Cov.: 28 AF XY: 0.0332 AC XY: 2216 AN XY: 66704

African (AFR) AF: 0.128 AC: 4481 AN: 35036

American (AMR) AF: 0.0156 AC: 213 AN: 13656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3254

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

South Asian (SAS) AF: 0.000223 AC: 1 AN: 4490

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9222

Middle Eastern (MID) AF: 0.0113 AC: 3 AN: 266

European-Non Finnish (NFE) AF: 0.000612 AC: 39 AN: 63676

Other (OTH) AF: 0.0228 AC: 43 AN: 1882

Alfa AF: 0.000503 Hom.: 0

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		1.0
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: rs757344904; hg19: chr12-105260193;