12-51026381-C-G

Variant names:

• chr12-51026381-C-G
• rs6580779
• NM_000617.3:c.-110G>C

Variant summary

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

The NM_000617.3(SLC11A2):​c.-110G>C variant causes a 5 prime UTR premature start codon gain 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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC11A2 NM_000617.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252
• Publications: 9 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=-0.77).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC11A2	NM_000617.3	c.-110G>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 16	ENST00000262052.9	NP_000608.1
SLC11A2	NM_000617.3	c.-110G>C		5_prime_UTR_variant	Exon 1 of 16	ENST00000262052.9	NP_000608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC11A2	ENST00000262052.9	c.-110G>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 16	1	NM_000617.3	ENSP00000262052.5
SLC11A2	ENST00000262052.9	c.-110G>C		5_prime_UTR_variant	Exon 1 of 16	1	NM_000617.3	ENSP00000262052.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1126160 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 552644

African (AFR) AF: 0.00 AC: 0 AN: 24062

American (AMR) AF: 0.00 AC: 0 AN: 28040

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15830

East Asian (EAS) AF: 0.00 AC: 0 AN: 12660

South Asian (SAS) AF: 0.00 AC: 0 AN: 75728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12634

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 913448

Other (OTH) AF: 0.00 AC: 0 AN: 41010

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.2
DANN	Benign	0.25
PhyloP100		-0.25
PromoterAI		-0.022	Neutral

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: rs6580779; hg19: chr12-51420164;