12-104805069-G-T

Variant names:

• chr12-104805069-G-T
• rs12298260
• NM_001352171.3:c.*83C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001352171.3(SLC41A2):​c.*83C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000932 in 1,072,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.3e-7 (0 hom.)
• Consequence: SLC41A2 NM_001352171.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71
• Publications: 0 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]

ENSG00000309266 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

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.*83C>A		3_prime_UTR	Exon 11 of 11	NP_001339100.1	Q96JW4
	SLC41A2	NM_001352169.2		c.*83C>A		3_prime_UTR	Exon 12 of 12	NP_001339098.1	Q96JW4
	SLC41A2	NM_001352170.3		c.*83C>A		3_prime_UTR	Exon 12 of 12	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.*83C>A		3_prime_UTR	Exon 11 of 11	ENSP00000258538.3	Q96JW4
	SLC41A2	ENST00000906846.1		c.*83C>A		3_prime_UTR	Exon 11 of 11	ENSP00000576905.1
	SLC41A2	ENST00000906847.1		c.*83C>A		3_prime_UTR	Exon 11 of 11	ENSP00000576906.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.32e-7 AC: 1 AN: 1072956 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 533354

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

African (AFR) AF: 0.00 AC: 0 AN: 23598

American (AMR) AF: 0.00 AC: 0 AN: 25930

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17354

East Asian (EAS) AF: 0.00 AC: 0 AN: 34812

South Asian (SAS) AF: 0.00 AC: 0 AN: 52450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3122

European-Non Finnish (NFE) AF: 0.00000121 AC: 1 AN: 825444

Other (OTH) AF: 0.00 AC: 0 AN: 45802

⚠️ 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 Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.55
PhyloP100		1.7

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: rs12298260; hg19: chr12-105198847;