12-50987935-C-A

Variant names:

• chr12-50987935-C-A
• rs224446
• NM_000617.3:c.*390G>T

Variant summary

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

The NM_001174125.2(SLC11A2):​c.*390G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC11A2 NM_001174125.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.576
• Publications: 14 publications found

Genes affected

SLC11A2 (HGNC:10908): (solute carrier family 11 member 2) This gene encodes a member of the solute carrier family 11 protein family. The product of this gene transports divalent metals and is involved in iron absorption. Mutations in this gene are associated with hypochromic microcytic anemia with iron overload. A related solute carrier family 11 protein gene is located on chromosome 2. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Apr 2010]

SLC11A2 Gene-Disease associations (from GenCC):

• microcytic anemia with liver iron overload

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp

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=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001174125.2. 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
	SLC11A2	NM_000617.3	MANE Select	c.*390G>T		3_prime_UTR	Exon 16 of 16	NP_000608.1
	SLC11A2	NM_001174125.2		c.*390G>T		3_prime_UTR	Exon 16 of 16	NP_001167596.1
	SLC11A2	NM_001379455.1		c.*390G>T		3_prime_UTR	Exon 17 of 17	NP_001366384.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC11A2	ENST00000262052.9	TSL:1 MANE Select	c.*390G>T		3_prime_UTR	Exon 16 of 16	ENSP00000262052.5
	SLC11A2	ENST00000394904.9	TSL:1	c.*390G>T		3_prime_UTR	Exon 16 of 16	ENSP00000378364.3
	SLC11A2	ENST00000547198.5	TSL:1	c.1629+447G>T		intron	N/A	ENSP00000446769.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1127684 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 553102

African (AFR) AF: 0.00 AC: 0 AN: 24102

American (AMR) AF: 0.00 AC: 0 AN: 27578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15950

East Asian (EAS) AF: 0.00 AC: 0 AN: 12894

South Asian (SAS) AF: 0.00 AC: 0 AN: 74758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12688

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 915852

Other (OTH) AF: 0.00 AC: 0 AN: 41120

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.6
DANN	Benign	0.54
PhyloP100		0.58

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: rs224446; hg19: chr12-51381718;