X-74421510-A-G
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_006517.5(SLC16A2):c.-128A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000287 in 905,672 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.000030 ( 0 hom. 6 hem. )
Consequence
SLC16A2
NM_006517.5 5_prime_UTR
NM_006517.5 5_prime_UTR
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 0.424
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 -8 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BS2
High Hemizygotes in GnomAdExome4 at 6 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC16A2 | NM_006517.5 | c.-128A>G | 5_prime_UTR_variant | 1/6 | ENST00000587091.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC16A2 | ENST00000587091.6 | c.-128A>G | 5_prime_UTR_variant | 1/6 | 1 | NM_006517.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000181 AC: 2AN: 110684Hom.: 0 Cov.: 23 AF XY: 0.0000303 AC XY: 1AN XY: 32974
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GnomAD3 exomes AF: 0.0000260 AC: 3AN: 115298Hom.: 0 AF XY: 0.0000265 AC XY: 1AN XY: 37782
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GnomAD4 exome AF: 0.0000302 AC: 24AN: 794988Hom.: 0 Cov.: 14 AF XY: 0.0000272 AC XY: 6AN XY: 220338
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GnomAD4 genome AF: 0.0000181 AC: 2AN: 110684Hom.: 0 Cov.: 23 AF XY: 0.0000303 AC XY: 1AN XY: 32974
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 28, 2022 | The c.95A>G (p.E32G) alteration is located in exon 1 (coding exon 1) of the SLC16A2 gene. This alteration results from a A to G substitution at nucleotide position 95, causing the glutamic acid (E) at amino acid position 32 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
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