12-104866587-TAA-T

Variant names:

• chr12-104866587-TAA-T
• rs34984157
• NM_001352171.3:c.1028-10_1028-9delTT

Variant summary

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

The NM_001352171.3(SLC41A2):​c.1028-10_1028-9delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,290,512 control chromosomes in the GnomAD database, including 3,890 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (3133 hom., cov: 0)
  • Exomes 𝑓: 0.22 (757 hom.)
• Consequence: SLC41A2 NM_001352171.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.06
• 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-TAA-T is Benign according to our data. Variant chr12-104866587-TAA-T is described in ClinVar as Benign. ClinVar VariationId is 1228903.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 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.1028-10_1028-9delTT		intron	N/A	NP_001339100.1	Q96JW4
	SLC41A2	NM_001352169.2		c.1028-10_1028-9delTT		intron	N/A	NP_001339098.1	Q96JW4
	SLC41A2	NM_001352170.3		c.1028-10_1028-9delTT		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.1028-10_1028-9delTT		intron	N/A	ENSP00000258538.3	Q96JW4
	SLC41A2	ENST00000906846.1		c.1028-10_1028-9delTT		intron	N/A	ENSP00000576905.1
	SLC41A2	ENST00000906847.1		c.1028-10_1028-9delTT		intron	N/A	ENSP00000576906.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 23008 AN: 138160 Hom.: 3131 Cov.: 0

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.0347

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0774

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0592

Gnomad OTH AF: 0.136

GnomAD2 exomes AF: 0.280 AC: 35111 AN: 125200 AF XY: 0.279

Gnomad AFR exome AF: 0.431

Gnomad AMR exome AF: 0.275

Gnomad ASJ exome AF: 0.297

Gnomad EAS exome AF: 0.287

Gnomad FIN exome AF: 0.260

Gnomad NFE exome AF: 0.268

Gnomad OTH exome AF: 0.280

GnomAD4 exome AF: 0.223 AC: 256901 AN: 1152322 Hom.: 757 AF XY: 0.224 AC XY: 128288 AN XY: 573546

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

African (AFR) AF: 0.415 AC: 10846 AN: 26144

American (AMR) AF: 0.266 AC: 7010 AN: 26364

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 5254 AN: 19520

East Asian (EAS) AF: 0.275 AC: 9734 AN: 35456

South Asian (SAS) AF: 0.209 AC: 12636 AN: 60342

European-Finnish (FIN) AF: 0.237 AC: 8283 AN: 34890

Middle Eastern (MID) AF: 0.245 AC: 954 AN: 3896

European-Non Finnish (NFE) AF: 0.212 AC: 190732 AN: 898048

Other (OTH) AF: 0.240 AC: 11452 AN: 47662

⚠️ 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: 0.167 AC: 23042 AN: 138190 Hom.: 3133 Cov.: 0 AF XY: 0.168 AC XY: 11197 AN XY: 66626

African (AFR) AF: 0.384 AC: 14642 AN: 38114

American (AMR) AF: 0.113 AC: 1555 AN: 13768

Ashkenazi Jewish (ASJ) AF: 0.0774 AC: 255 AN: 3296

East Asian (EAS) AF: 0.254 AC: 1232 AN: 4844

South Asian (SAS) AF: 0.103 AC: 444 AN: 4290

European-Finnish (FIN) AF: 0.111 AC: 831 AN: 7478

Middle Eastern (MID) AF: 0.129 AC: 32 AN: 248

European-Non Finnish (NFE) AF: 0.0592 AC: 3758 AN: 63434

Other (OTH) AF: 0.140 AC: 264 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		1.1
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;