X-74421631-CGCCGCGATGGCGCTGCAAAGCCAGGCGAGCGAGGAAGCAAAGGGGCCCTGGCAGGAGGCAGACCAGGAACAGCAGGAGCCGGTGGGTAGCCCAGAGCCGGAGTCTGAGCCGGAGCCTGAGCCCGAGCCCGAGCCCGTGCCAGTGCCCCCGCCCGAGCCCCAGCCGGAGCCCCAGCCCCTACCGGACCCCGCACCCCTGCCGGAGCTGGAGTTCGAGTCCGAGCGGGTGCACGAACCCGAGCCCACGCCTACGGTAGAGACCCGCGGCACCGCGCGCGGCTTCCAGCCTCCCGAAGGTGGCTTCGGCTGGGTGGTGGTGTTCGCTGCCACCTGGTGCAACGGCTCCATCTTCGGCATCCATAACTCTGTCGGGATCCTCTACTCCATGCTGCTAGAGGAGGAAAAGGAAAAAAATCGCCAAGTGGAGTTCCAAGCAGGTGAG-C
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_006517.5(SLC16A2):c.-6_430+5del variant causes a splice donor, splice donor 5th base, coding sequence, 5 prime UTR, intron change involving the alteration of a non-conserved nucleotide. 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
NM_006517.5 splice_donor, splice_donor_5th_base, coding_sequence, 5_prime_UTR, intron
NM_006517.5 splice_donor, splice_donor_5th_base, coding_sequence, 5_prime_UTR, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.39
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 Pathogenic. Variant got 12 ACMG points.
PVS1
Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease,
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-74421631-CGCCGCGATGGCGCTGCAAAGCCAGGCGAGCGAGGAAGCAAAGGGGCCCTGGCAGGAGGCAGACCAGGAACAGCAGGAGCCGGTGGGTAGCCCAGAGCCGGAGTCTGAGCCGGAGCCTGAGCCCGAGCCCGAGCCCGTGCCAGTGCCCCCGCCCGAGCCCCAGCCGGAGCCCCAGCCCCTACCGGACCCCGCACCCCTGCCGGAGCTGGAGTTCGAGTCCGAGCGGGTGCACGAACCCGAGCCCACGCCTACGGTAGAGACCCGCGGCACCGCGCGCGGCTTCCAGCCTCCCGAAGGTGGCTTCGGCTGGGTGGTGGTGTTCGCTGCCACCTGGTGCAACGGCTCCATCTTCGGCATCCATAACTCTGTCGGGATCCTCTACTCCATGCTGCTAGAGGAGGAAAAGGAAAAAAATCGCCAAGTGGAGTTCCAAGCAGGTGAG-C is Pathogenic according to our data. Variant chrX-74421631-CGCCGCGATGGCGCTGCAAAGCCAGGCGAGCGAGGAAGCAAAGGGGCCCTGGCAGGAGGCAGACCAGGAACAGCAGGAGCCGGTGGGTAGCCCAGAGCCGGAGTCTGAGCCGGAGCCTGAGCCCGAGCCCGAGCCCGTGCCAGTGCCCCCGCCCGAGCCCCAGCCGGAGCCCCAGCCCCTACCGGACCCCGCACCCCTGCCGGAGCTGGAGTTCGAGTCCGAGCGGGTGCACGAACCCGAGCCCACGCCTACGGTAGAGACCCGCGGCACCGCGCGCGGCTTCCAGCCTCCCGAAGGTGGCTTCGGCTGGGTGGTGGTGTTCGCTGCCACCTGGTGCAACGGCTCCATCTTCGGCATCCATAACTCTGTCGGGATCCTCTACTCCATGCTGCTAGAGGAGGAAAAGGAAAAAAATCGCCAAGTGGAGTTCCAAGCAGGTGAG-C is described in ClinVar as [Pathogenic]. Clinvar id is 1077180.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC16A2 | NM_006517.5 | c.-6_430+5del | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, 5_prime_UTR_variant, intron_variant | 1/6 | ENST00000587091.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC16A2 | ENST00000587091.6 | c.-6_430+5del | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, 5_prime_UTR_variant, intron_variant | 1/6 | 1 | NM_006517.5 | P1 | ||
SLC16A2 | ENST00000636771.1 | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, 5_prime_UTR_variant, intron_variant, NMD_transcript_variant | 1/7 | 5 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD3 genomes
Cov.:
22
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 22
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 submitter | clinical testing | Genetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University | May 13, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.