rs797045962

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate

The ENST00000587091.6(SLC16A2):​c.1392dup​(p.Ile465HisfsTer52) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 22)

Consequence

SLC16A2
ENST00000587091.6 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 5.92
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 15 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-74529428-G-GC is Pathogenic according to our data. Variant chrX-74529428-G-GC is described in ClinVar as [Pathogenic]. Clinvar id is 212188.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC16A2NM_006517.5 linkuse as main transcriptc.1392dup p.Ile465HisfsTer52 frameshift_variant 5/6 ENST00000587091.6 NP_006508.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC16A2ENST00000587091.6 linkuse as main transcriptc.1392dup p.Ile465HisfsTer52 frameshift_variant 5/61 NM_006517.5 ENSP00000465734 P1
SLC16A2ENST00000590447.1 linkuse as main transcriptc.611-1899dup intron_variant 5 ENSP00000466213
SLC16A2ENST00000636771.1 linkuse as main transcriptc.*1093dup 3_prime_UTR_variant, NMD_transcript_variant 6/75 ENSP00000490445

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
22

ClinVar

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

Submissions by phenotype

Allan-Herndon-Dudley syndrome Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoFeb 08, 2013- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs797045962; hg19: chrX-73749263; API