NM_001352171.3:c.1175+49_1175+50delGT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001352171.3(SLC41A2):​c.1175+49_1175+50delGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0435 in 1,390,440 control chromosomes in the GnomAD database, including 67 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (57 hom., cov: 0)
  • Exomes 𝑓: 0.046 (10 hom.)
• Consequence: SLC41A2 NM_001352171.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 12-104866381-TAC-T is Benign according to our data. Variant chr12-104866381-TAC-T is described in ClinVar as Benign. ClinVar VariationId is 1258555.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0198 (2797/140962) while in subpopulation AFR AF = 0.0513 (1890/36810). AF 95% confidence interval is 0.0494. There are 57 homozygotes in GnomAd4. There are 1306 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 57 gene

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+49_1175+50delGT		intron	N/A	NP_001339100.1	Q96JW4
	SLC41A2	NM_001387131.1		c.1224_1225delGT	p.Tyr409ArgfsTer10	frameshift	Exon 7 of 7	NP_001374060.1
	SLC41A2	NM_001387132.1		c.1224_1225delGT	p.Tyr409ArgfsTer10	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+49_1175+50delGT		intron	N/A	ENSP00000258538.3	Q96JW4
	SLC41A2	ENST00000906846.1		c.1175+49_1175+50delGT		intron	N/A	ENSP00000576905.1
	SLC41A2	ENST00000906847.1		c.1175+49_1175+50delGT		intron	N/A	ENSP00000576906.1

Frequencies

GnomAD3 genomes AF: 0.0198 AC: 2789 AN: 140870 Hom.: 57 Cov.: 0

Gnomad AFR AF: 0.0514

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0106

Gnomad ASJ AF: 0.00240

Gnomad EAS AF: 0.00805

Gnomad SAS AF: 0.0156

Gnomad FIN AF: 0.00509

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00865

Gnomad OTH AF: 0.0156

GnomAD2 exomes AF: 0.0682 AC: 10314 AN: 151248 AF XY: 0.0696

Gnomad AFR exome AF: 0.0612

Gnomad AMR exome AF: 0.0582

Gnomad ASJ exome AF: 0.0417

Gnomad EAS exome AF: 0.0682

Gnomad FIN exome AF: 0.0642

Gnomad NFE exome AF: 0.0655

Gnomad OTH exome AF: 0.0620

GnomAD4 exome AF: 0.0462 AC: 57666 AN: 1249478 Hom.: 10 AF XY: 0.0472 AC XY: 28970 AN XY: 614338

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

African (AFR) AF: 0.0597 AC: 1679 AN: 28106

American (AMR) AF: 0.0490 AC: 1536 AN: 31320

Ashkenazi Jewish (ASJ) AF: 0.0300 AC: 610 AN: 20316

East Asian (EAS) AF: 0.0455 AC: 1606 AN: 35312

South Asian (SAS) AF: 0.0836 AC: 4572 AN: 54670

European-Finnish (FIN) AF: 0.0517 AC: 2074 AN: 40098

Middle Eastern (MID) AF: 0.0299 AC: 138 AN: 4610

European-Non Finnish (NFE) AF: 0.0437 AC: 43026 AN: 983728

Other (OTH) AF: 0.0473 AC: 2425 AN: 51318

⚠️ 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: 0.0198 AC: 2797 AN: 140962 Hom.: 57 Cov.: 0 AF XY: 0.0190 AC XY: 1306 AN XY: 68612

African (AFR) AF: 0.0513 AC: 1890 AN: 36810

American (AMR) AF: 0.0106 AC: 152 AN: 14310

Ashkenazi Jewish (ASJ) AF: 0.00240 AC: 8 AN: 3328

East Asian (EAS) AF: 0.00807 AC: 38 AN: 4708

South Asian (SAS) AF: 0.0159 AC: 67 AN: 4218

European-Finnish (FIN) AF: 0.00509 AC: 49 AN: 9626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 270

European-Non Finnish (NFE) AF: 0.00865 AC: 561 AN: 64884

Other (OTH) AF: 0.0165 AC: 32 AN: 1944

Alfa AF: 0.0499 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		-0.60
Mutation Taster		=100/0	polymorphism

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; COSMIC: COSV51605412;