rs200444038
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_006517.5(SLC16A2):c.447C>T(p.Leu149=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000864 in 1,209,865 control chromosomes in the GnomAD database, including 3 homozygotes. There are 326 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.00065 ( 1 hom., 24 hem., cov: 23)
Exomes 𝑓: 0.00089 ( 2 hom. 302 hem. )
Consequence
SLC16A2
NM_006517.5 synonymous
NM_006517.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.814
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 Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
?
Variant X-74521006-C-T is Benign according to our data. Variant chrX-74521006-C-T is described in ClinVar as [Benign]. Clinvar id is 436734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.814 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000653 (73/111795) while in subpopulation NFE AF= 0.000884 (47/53179). AF 95% confidence interval is 0.000682. There are 1 homozygotes in gnomad4. There are 24 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAd4 at 24 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC16A2 | NM_006517.5 | c.447C>T | p.Leu149= | synonymous_variant | 2/6 | ENST00000587091.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC16A2 | ENST00000587091.6 | c.447C>T | p.Leu149= | synonymous_variant | 2/6 | 1 | NM_006517.5 | P1 | |
SLC16A2 | ENST00000636771.1 | c.*148C>T | 3_prime_UTR_variant, NMD_transcript_variant | 3/7 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000653 AC: 73AN: 111795Hom.: 1 Cov.: 23 AF XY: 0.000707 AC XY: 24AN XY: 33961
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GnomAD3 exomes AF: 0.000698 AC: 128AN: 183408Hom.: 1 AF XY: 0.000649 AC XY: 44AN XY: 67846
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GnomAD4 exome AF: 0.000885 AC: 972AN: 1098070Hom.: 2 Cov.: 31 AF XY: 0.000831 AC XY: 302AN XY: 363424
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GnomAD4 genome ? AF: 0.000653 AC: 73AN: 111795Hom.: 1 Cov.: 23 AF XY: 0.000707 AC XY: 24AN XY: 33961
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 14, 2017 | - - |
Spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 09, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at