NM_006517.5:c.359C>T
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_006517.5(SLC16A2):c.359C>T(p.Ser120Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).
Frequency
Genomes: not found (cov: 24)
Consequence
SLC16A2
NM_006517.5 missense
NM_006517.5 missense
Scores
5
8
Clinical Significance
Conservation
PhyloP100: 6.72
Publications
4 publications found
Genes affected
SLC16A2 (HGNC:10923): (solute carrier family 16 member 2) This gene encodes an integral membrane protein that functions as a transporter of thyroid hormone. The encoded protein facilitates the cellular importation of thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3) and diidothyronine (T2). This gene is expressed in many tissues and likely plays an important role in the development of the central nervous system. Loss of function mutations in this gene are associated with psychomotor retardation in males while females exhibit no neurological defects and more moderate thyroid-deficient phenotypes. This gene is subject to X-chromosome inactivation. Mutations in this gene are the cause of Allan-Herndon-Dudley syndrome. [provided by RefSeq, Mar 2012]
SLC16A2 Gene-Disease associations (from GenCC):
- Allan-Herndon-Dudley syndromeInheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)
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ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 8 ACMG points.
PM1
In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 2 uncertain in NM_006517.5
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.969
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_006517.5. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SLC16A2 | TSL:1 MANE Select | c.359C>T | p.Ser120Phe | missense | Exon 1 of 6 | ENSP00000465734.1 | P36021 | ||
| SLC16A2 | c.359C>T | p.Ser120Phe | missense | Exon 1 of 7 | ENSP00000548651.1 | ||||
| SLC16A2 | c.359C>T | p.Ser120Phe | missense | Exon 1 of 7 | ENSP00000592906.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
24
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
GnomAD4 genome
Cov.:
24
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions
View on ClinVar Significance:not provided
Revision:no classification provided
Pathogenic
VUS
Benign
Condition
-
-
-
Allan-Herndon-Dudley syndrome (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M
PhyloP100
PrimateAI
Uncertain
T
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of helix (P = 0.2059)
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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