X-74531529-C-T

Position:

chrX-74531529-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BS1BS2

The NM_006517.5(SLC16A2):c.1596C>T(p.Ser532Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000843 in 1,207,168 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 313 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., 12 hem., cov: 23)

Exomes 𝑓: 0.00087 ( 0 hom. 301 hem. )

Consequence

SLC16A2
NM_006517.5 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: -0.0880

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]

SLC16A2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant X-74531529-C-T is Benign according to our data. Variant chrX-74531529-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 167692.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1, Benign=3}. Variant chrX-74531529-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.088 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000553 (62/112067) while in subpopulation NFE AF= 0.00094 (50/53166). AF 95% confidence interval is 0.000733. There are 0 homozygotes in gnomad4. There are 12 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 12 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC16A2	NM_006517.5 linkuse as main transcript	c.1596C>T	p.Ser532Ser	synonymous_variant	6/6	ENST00000587091.6	NP_006508.2	P36021

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC16A2	ENST00000587091.6 linkuse as main transcript	c.1596C>T	p.Ser532Ser	synonymous_variant	6/6	1	NM_006517.5	ENSP00000465734.1	P36021
SLC16A2	ENST00000590447.1 linkuse as main transcript	c.*119C>T		3_prime_UTR_variant	4/4	5		ENSP00000466213.1	K7ELT4
SLC16A2	ENST00000636771.1 linkuse as main transcript	n.*1297C>T		non_coding_transcript_exon_variant	7/7	5		ENSP00000490445.1	A0A1B0GVB4
SLC16A2	ENST00000636771.1 linkuse as main transcript	n.*1297C>T		3_prime_UTR_variant	7/7	5		ENSP00000490445.1	A0A1B0GVB4

Frequencies

GnomAD3 genomes

AF:

0.000554

AC:

AN:

112011

Hom.:

Cov.:

AF XY:

0.000351

AC XY:

AN XY:

34179

show subpopulations

Gnomad AFR

AF:

0.0000974

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000566

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000163

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000940

Gnomad OTH

AF:

0.00134

GnomAD3 exomes

AF:

0.000534

AC:

AN:

183361

Hom.:

AF XY:

0.000590

AC XY:

AN XY:

67819

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.000182

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000524

Gnomad FIN exome

AF:

0.0000625

Gnomad NFE exome

AF:

0.00104

Gnomad OTH exome

AF:

0.00110

GnomAD4 exome

AF:

0.000873

AC:

956

AN:

1095101

Hom.:

Cov.:

AF XY:

0.000834

AC XY:

301

AN XY:

361123

show subpopulations

Gnomad4 AFR exome

AF:

0.000342

Gnomad4 AMR exome

AF:

0.000341

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000740

Gnomad4 FIN exome

AF:

0.000123

Gnomad4 NFE exome

AF:

0.00108

Gnomad4 OTH exome

AF:

0.000392

GnomAD4 genome

AF:

0.000553

AC:

AN:

112067

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

AN XY:

34245

show subpopulations

Gnomad4 AFR

AF:

0.0000972

Gnomad4 AMR

AF:

0.000566

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000163

Gnomad4 NFE

AF:

0.000940

Gnomad4 OTH

AF:

0.00132

Alfa

AF:

0.000546

Hom.:

Bravo

AF:

0.000525

EpiCase

AF:

0.00180

EpiControl

AF:

0.00124

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2019	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 06, 2014	- -

Spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 17, 2024

- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Mar 28, 2016

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 13, 2017

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Hereditary spastic paraplegia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jan 31, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

3.1

DANN

Benign

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over