12-104866587-TAAAAAAAAA-TAAAAA

Variant names:

• chr12-104866587-TAAAA-T
• rs34984157
• NM_001352171.3:c.1028-12_1028-9delTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001352171.3(SLC41A2):​c.1028-12_1028-9delTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00257 in 1,333,796 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000036 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0029 (0 hom.)
• Consequence: SLC41A2 NM_001352171.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82
• Publications: 1 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Variant has high frequency in the EAS (0.0196) population. However there is too low homozygotes in high coverage region: (expected more than 2, got 0).

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.1028-12_1028-9delTTTT		intron	N/A	NP_001339100.1	Q96JW4
	SLC41A2	NM_001352169.2		c.1028-12_1028-9delTTTT		intron	N/A	NP_001339098.1	Q96JW4
	SLC41A2	NM_001352170.3		c.1028-12_1028-9delTTTT		intron	N/A	NP_001339099.1	Q96JW4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC41A2	ENST00000258538.8	TSL:1 MANE Select	c.1028-12_1028-9delTTTT		intron	N/A	ENSP00000258538.3	Q96JW4
	SLC41A2	ENST00000906846.1		c.1028-12_1028-9delTTTT		intron	N/A	ENSP00000576905.1
	SLC41A2	ENST00000906847.1		c.1028-12_1028-9delTTTT		intron	N/A	ENSP00000576906.1

Frequencies

GnomAD3 genomes AF: 0.0000362 AC: 5 AN: 138216 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000263

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000206

Gnomad SAS AF: 0.000232

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000315

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00782 AC: 979 AN: 125200 AF XY: 0.00752

Gnomad AFR exome AF: 0.00708

Gnomad AMR exome AF: 0.0140

Gnomad ASJ exome AF: 0.00682

Gnomad EAS exome AF: 0.0247

Gnomad FIN exome AF: 0.00474

Gnomad NFE exome AF: 0.00389

Gnomad OTH exome AF: 0.00723

GnomAD4 exome AF: 0.00286 AC: 3425 AN: 1195580 Hom.: 0 AF XY: 0.00299 AC XY: 1776 AN XY: 594698

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

African (AFR) AF: 0.00594 AC: 157 AN: 26448

American (AMR) AF: 0.0102 AC: 274 AN: 26882

Ashkenazi Jewish (ASJ) AF: 0.00369 AC: 75 AN: 20298

East Asian (EAS) AF: 0.0208 AC: 748 AN: 35890

South Asian (SAS) AF: 0.00540 AC: 333 AN: 61678

European-Finnish (FIN) AF: 0.00351 AC: 126 AN: 35868

Middle Eastern (MID) AF: 0.00275 AC: 11 AN: 4000

European-Non Finnish (NFE) AF: 0.00166 AC: 1549 AN: 935148

Other (OTH) AF: 0.00308 AC: 152 AN: 49368

⚠️ 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: 0.0000362 AC: 5 AN: 138216 Hom.: 0 Cov.: 0 AF XY: 0.0000300 AC XY: 2 AN XY: 66600

African (AFR) AF: 0.0000263 AC: 1 AN: 38052

American (AMR) AF: 0.00 AC: 0 AN: 13768

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3296

East Asian (EAS) AF: 0.000206 AC: 1 AN: 4862

South Asian (SAS) AF: 0.000232 AC: 1 AN: 4318

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7478

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 274

European-Non Finnish (NFE) AF: 0.0000315 AC: 2 AN: 63468

Other (OTH) AF: 0.00 AC: 0 AN: 1864

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.8
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: rs34984157; hg19: chr12-105260365;