chr12-104866587-T-TAAAAAAAAAAAAAAAA

Variant names:

• chr12-104866587-T-TAAAAAAAAAAAAAAAA
• rs34984157
• NM_001352171.3:c.1028-24_1028-9dupTTTTTTTTTTTTTTTT

Variant summary

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

The NM_001352171.3(SLC41A2):​c.1028-24_1028-9dupTTTTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_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 0.000014 (0 hom., cov: 0)
• Consequence: SLC41A2 NM_001352171.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.272
• 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 0 ACMG points.

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.1028-24_1028-9dupTTTTTTTTTTTTTTTT		intron	N/A	NP_001339100.1	Q96JW4
	SLC41A2	NM_001352169.2		c.1028-24_1028-9dupTTTTTTTTTTTTTTTT		intron	N/A	NP_001339098.1	Q96JW4
	SLC41A2	NM_001352170.3		c.1028-24_1028-9dupTTTTTTTTTTTTTTTT		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.1028-9_1028-8insTTTTTTTTTTTTTTTT		intron	N/A	ENSP00000258538.3	Q96JW4
	SLC41A2	ENST00000906846.1		c.1028-9_1028-8insTTTTTTTTTTTTTTTT		intron	N/A	ENSP00000576905.1
	SLC41A2	ENST00000906847.1		c.1028-9_1028-8insTTTTTTTTTTTTTTTT		intron	N/A	ENSP00000576906.1

Frequencies

GnomAD3 genomes AF: 0.0000145 AC: 2 AN: 138224 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000315

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000145 AC: 2 AN: 138224 Hom.: 0 Cov.: 0 AF XY: 0.0000150 AC XY: 1 AN XY: 66602

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

African (AFR) AF: 0.00 AC: 0 AN: 38052

American (AMR) AF: 0.00 AC: 0 AN: 13770

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4862

South Asian (SAS) AF: 0.00 AC: 0 AN: 4318

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7480

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

European-Non Finnish (NFE) AF: 0.0000315 AC: 2 AN: 63470

Other (OTH) AF: 0.00 AC: 0 AN: 1866

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000000983081), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.27

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34984157; hg19: chr12-105260365;