chr2-218383023-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000578.4(SLC11A1):​c.71C>T​(p.Pro24Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000576 in 1,614,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

SLC11A1
NM_000578.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.183
Variant links:
Genes affected
SLC11A1 (HGNC:10907): (solute carrier family 11 member 1) This gene is a member of the solute carrier family 11 (proton-coupled divalent metal ion transporters) family and encodes a multi-pass membrane protein. The protein functions as a divalent transition metal (iron and manganese) transporter involved in iron metabolism and host resistance to certain pathogens. Mutations in this gene have been associated with susceptibility to infectious diseases such as tuberculosis and leprosy, and inflammatory diseases such as rheumatoid arthritis and Crohn disease. Alternatively spliced variants that encode different protein isoforms have been described but the full-length nature of only one has been determined. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.008055091).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC11A1NM_000578.4 linkuse as main transcriptc.71C>T p.Pro24Leu missense_variant 2/15 ENST00000233202.11 NP_000569.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC11A1ENST00000233202.11 linkuse as main transcriptc.71C>T p.Pro24Leu missense_variant 2/151 NM_000578.4 ENSP00000233202 P1P49279-1

Frequencies

GnomAD3 genomes
AF:
0.000256
AC:
39
AN:
152066
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000846
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000965
AC:
24
AN:
248720
Hom.:
0
AF XY:
0.0000891
AC XY:
12
AN XY:
134670
show subpopulations
Gnomad AFR exome
AF:
0.000986
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000180
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000369
AC:
54
AN:
1461864
Hom.:
0
Cov.:
31
AF XY:
0.0000316
AC XY:
23
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.00102
Gnomad4 AMR exome
AF:
0.000157
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.00000629
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.000256
AC:
39
AN:
152184
Hom.:
0
Cov.:
31
AF XY:
0.000255
AC XY:
19
AN XY:
74410
show subpopulations
Gnomad4 AFR
AF:
0.000843
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.0000966
Hom.:
0
Bravo
AF:
0.000302
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000115
AC:
14
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 31, 2024The c.71C>T (p.P24L) alteration is located in exon 2 (coding exon 2) of the SLC11A1 gene. This alteration results from a C to T substitution at nucleotide position 71, causing the proline (P) at amino acid position 24 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.080
BayesDel_addAF
Benign
-0.61
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
14
DANN
Uncertain
0.99
DEOGEN2
Benign
0.18
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.037
N
LIST_S2
Benign
0.43
T
M_CAP
Benign
0.0033
T
MetaRNN
Benign
0.0081
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.46
N
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.81
N
REVEL
Benign
0.012
Sift
Benign
0.16
T
Sift4G
Benign
0.064
T
Polyphen
0.0010
B
Vest4
0.13
MVP
0.36
MPC
0.12
ClinPred
0.0040
T
GERP RS
0.92
Varity_R
0.029
gMVP
0.52

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs142054519; hg19: chr2-219247746; API