12-104866381-TACACACACACACACACACACAC-TACACACACAC

Variant names:

• chr12-104866381-TACACACACACAC-T
• rs57548373
• NM_001352171.3:c.1175+39_1175+50delGTGTGTGTGTGT

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_001387131.1(SLC41A2):​c.1214_1225delGTGTGTGTGTGT​(p.Cys405_Val408del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000283 in 1,427,030 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00079 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: SLC41A2 NM_001387131.1 disruptive_inframe_deletion
• 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: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001387131.1

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+39_1175+50delGTGTGTGTGTGT		intron	N/A	NP_001339100.1	Q96JW4
	SLC41A2	NM_001387131.1		c.1214_1225delGTGTGTGTGTGT	p.Cys405_Val408del	disruptive_inframe_deletion	Exon 7 of 7	NP_001374060.1
	SLC41A2	NM_001387132.1		c.1214_1225delGTGTGTGTGTGT	p.Cys405_Val408del	disruptive_inframe_deletion	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+39_1175+50delGTGTGTGTGTGT		intron	N/A	ENSP00000258538.3	Q96JW4
	SLC41A2	ENST00000906846.1		c.1175+39_1175+50delGTGTGTGTGTGT		intron	N/A	ENSP00000576905.1
	SLC41A2	ENST00000906847.1		c.1175+39_1175+50delGTGTGTGTGTGT		intron	N/A	ENSP00000576906.1

Frequencies

GnomAD3 genomes AF: 0.000787 AC: 111 AN: 141012 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00237

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000699

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00339

Gnomad SAS AF: 0.000237

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000770

Gnomad OTH AF: 0.000518

GnomAD4 exome AF: 0.000228 AC: 293 AN: 1285926 Hom.: 0 AF XY: 0.000223 AC XY: 141 AN XY: 631918

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

African (AFR) AF: 0.00294 AC: 84 AN: 28548

American (AMR) AF: 0.000252 AC: 8 AN: 31780

Ashkenazi Jewish (ASJ) AF: 0.0000971 AC: 2 AN: 20606

East Asian (EAS) AF: 0.00117 AC: 42 AN: 35862

South Asian (SAS) AF: 0.000337 AC: 19 AN: 56370

European-Finnish (FIN) AF: 0.0000733 AC: 3 AN: 40918

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4702

European-Non Finnish (NFE) AF: 0.000115 AC: 117 AN: 1014552

Other (OTH) AF: 0.000342 AC: 18 AN: 52588

⚠️ 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: 0.000787 AC: 111 AN: 141104 Hom.: 0 Cov.: 0 AF XY: 0.000786 AC XY: 54 AN XY: 68670

African (AFR) AF: 0.00236 AC: 87 AN: 36836

American (AMR) AF: 0.0000698 AC: 1 AN: 14326

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3330

East Asian (EAS) AF: 0.00340 AC: 16 AN: 4710

South Asian (SAS) AF: 0.000237 AC: 1 AN: 4222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9668

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

European-Non Finnish (NFE) AF: 0.0000770 AC: 5 AN: 64932

Other (OTH) AF: 0.000514 AC: 1 AN: 1946

Alfa AF: 0.00 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;