12-104866587-TAAAAAAAAA-TAAAAAA

Variant names:

• chr12-104866587-TAAA-T
• rs34984157
• NM_001352171.3:c.1028-11_1028-9delTTT

Variant summary

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

The NM_001352171.3(SLC41A2):​c.1028-11_1028-9delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0339 in 1,308,236 control chromosomes in the GnomAD database, including 71 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0092 (33 hom., cov: 0)
  • Exomes 𝑓: 0.037 (38 hom.)
• Consequence: SLC41A2 NM_001352171.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 12-104866587-TAAA-T is Benign according to our data. Variant chr12-104866587-TAAA-T is described in ClinVar as Benign. ClinVar VariationId is 1286792.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.112 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.1028-11_1028-9delTTT		intron	N/A	NP_001339100.1	Q96JW4
	SLC41A2	NM_001352169.2		c.1028-11_1028-9delTTT		intron	N/A	NP_001339098.1	Q96JW4
	SLC41A2	NM_001352170.3		c.1028-11_1028-9delTTT		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.1028-11_1028-9delTTT		intron	N/A	ENSP00000258538.3	Q96JW4
	SLC41A2	ENST00000906846.1		c.1028-11_1028-9delTTT		intron	N/A	ENSP00000576905.1
	SLC41A2	ENST00000906847.1		c.1028-11_1028-9delTTT		intron	N/A	ENSP00000576906.1

Frequencies

GnomAD3 genomes AF: 0.00914 AC: 1263 AN: 138188 Hom.: 32 Cov.: 0

Gnomad AFR AF: 0.00221

Gnomad AMI AF: 0.00598

Gnomad AMR AF: 0.0208

Gnomad ASJ AF: 0.000607

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.00831

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00246

Gnomad OTH AF: 0.0113

GnomAD2 exomes AF: 0.0719 AC: 9007 AN: 125200 AF XY: 0.0691

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.101

Gnomad ASJ exome AF: 0.0653

Gnomad EAS exome AF: 0.178

Gnomad FIN exome AF: 0.0499

Gnomad NFE exome AF: 0.0462

Gnomad OTH exome AF: 0.0613

GnomAD4 exome AF: 0.0368 AC: 43094 AN: 1170016 Hom.: 38 AF XY: 0.0378 AC XY: 21981 AN XY: 581992

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

African (AFR) AF: 0.0864 AC: 2233 AN: 25844

American (AMR) AF: 0.0877 AC: 2320 AN: 26452

Ashkenazi Jewish (ASJ) AF: 0.0460 AC: 909 AN: 19752

East Asian (EAS) AF: 0.182 AC: 6453 AN: 35500

South Asian (SAS) AF: 0.0515 AC: 3130 AN: 60798

European-Finnish (FIN) AF: 0.0443 AC: 1562 AN: 35242

Middle Eastern (MID) AF: 0.0350 AC: 137 AN: 3910

European-Non Finnish (NFE) AF: 0.0265 AC: 24244 AN: 914324

Other (OTH) AF: 0.0437 AC: 2106 AN: 48194

⚠️ 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: 0.00920 AC: 1271 AN: 138220 Hom.: 33 Cov.: 0 AF XY: 0.0102 AC XY: 681 AN XY: 66628

African (AFR) AF: 0.00228 AC: 87 AN: 38122

American (AMR) AF: 0.0211 AC: 291 AN: 13782

Ashkenazi Jewish (ASJ) AF: 0.000607 AC: 2 AN: 3294

East Asian (EAS) AF: 0.120 AC: 581 AN: 4852

South Asian (SAS) AF: 0.0154 AC: 66 AN: 4292

European-Finnish (FIN) AF: 0.00831 AC: 62 AN: 7460

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 246

European-Non Finnish (NFE) AF: 0.00246 AC: 156 AN: 63454

Other (OTH) AF: 0.0112 AC: 21 AN: 1882

Alfa AF: 0.00 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		1.8
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: rs34984157; hg19: chr12-105260365;