12-104894066-G-A

Variant names:

• chr12-104894066-G-A
• rs10778354
• NM_001352171.3:c.735+1208C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001352171.3(SLC41A2):​c.735+1208C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 151,898 control chromosomes in the GnomAD database, including 19,723 homozygotes. 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: 𝑓 0.50 (19723 hom., cov: 31)
• Consequence: SLC41A2 NM_001352171.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.359
• 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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.521 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC41A2	NM_001352171.3	MANE Select	c.735+1208C>T		intron	N/A	NP_001339100.1
	SLC41A2	NM_001352169.2		c.735+1208C>T		intron	N/A	NP_001339098.1
	SLC41A2	NM_001352170.3		c.735+1208C>T		intron	N/A	NP_001339099.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC41A2	ENST00000258538.8	TSL:1 MANE Select	c.735+1208C>T		intron	N/A	ENSP00000258538.3
	SLC41A2	ENST00000437220.1	TSL:5	c.300+1208C>T		intron	N/A	ENSP00000391377.1

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76601 AN: 151778 Hom.: 19707 Cov.: 31

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.534

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.505 AC: 76645 AN: 151898 Hom.: 19723 Cov.: 31 AF XY: 0.499 AC XY: 37059 AN XY: 74244

African (AFR) AF: 0.514 AC: 21274 AN: 41406

American (AMR) AF: 0.531 AC: 8106 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2136 AN: 3468

East Asian (EAS) AF: 0.235 AC: 1217 AN: 5176

South Asian (SAS) AF: 0.339 AC: 1629 AN: 4812

European-Finnish (FIN) AF: 0.477 AC: 5015 AN: 10514

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35540 AN: 67938

Other (OTH) AF: 0.531 AC: 1120 AN: 2110

Alfa AF: 0.514 Hom.: 2814

Bravo AF: 0.514

Asia WGS AF: 0.315 AC: 1095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Benign	0.94
PhyloP100		0.36
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: rs10778354; hg19: chr12-105287844;