X-74524656-A-T

Position:

chrX-74524656-A-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_006517.5(SLC16A2):c.873A>T(p.Pro291Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,209,790 control chromosomes in the GnomAD database, including 29 homozygotes. There are 562 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0084 ( 16 hom., 264 hem., cov: 22)

Exomes 𝑓: 0.00097 ( 13 hom. 298 hem. )

Consequence

SLC16A2
NM_006517.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: 1.39

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant X-74524656-A-T is Benign according to our data. Variant chrX-74524656-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 21460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-74524656-A-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.39 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0084 (937/111583) while in subpopulation AFR AF= 0.0289 (886/30667). AF 95% confidence interval is 0.0273. There are 16 homozygotes in gnomad4. There are 264 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC16A2	NM_006517.5 linkuse as main transcript	c.873A>T	p.Pro291Pro	synonymous_variant	3/6	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.873A>T	p.Pro291Pro	synonymous_variant	3/6	1	NM_006517.5	ENSP00000465734.1	P36021
SLC16A2	ENST00000590447.1 linkuse as main transcript	c.312A>T	p.Pro104Pro	synonymous_variant	2/4	5		ENSP00000466213.1	K7ELT4
SLC16A2	ENST00000636771.1 linkuse as main transcript	n.*574A>T		non_coding_transcript_exon_variant	4/7	5		ENSP00000490445.1	A0A1B0GVB4
SLC16A2	ENST00000636771.1 linkuse as main transcript	n.*574A>T		3_prime_UTR_variant	4/7	5		ENSP00000490445.1	A0A1B0GVB4

Frequencies

GnomAD3 genomes

AF:

0.00839

AC:

936

AN:

111528

Hom.:

Cov.:

AF XY:

0.00780

AC XY:

263

AN XY:

33732

show subpopulations

Gnomad AFR

AF:

0.0289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00408

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00422

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00398

GnomAD3 exomes

AF:

0.00250

AC:

459

AN:

183296

Hom.:

AF XY:

0.00183

AC XY:

124

AN XY:

67748

show subpopulations

Gnomad AFR exome

AF:

0.0309

Gnomad AMR exome

AF:

0.00157

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000524

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000367

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.000965

AC:

1060

AN:

1098207

Hom.:

Cov.:

AF XY:

0.000820

AC XY:

298

AN XY:

363565

show subpopulations

Gnomad4 AFR exome

AF:

0.0327

Gnomad4 AMR exome

AF:

0.00176

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000923

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000202

Gnomad4 OTH exome

AF:

0.00239

GnomAD4 genome

AF:

0.00840

AC:

937

AN:

111583

Hom.:

Cov.:

AF XY:

0.00781

AC XY:

264

AN XY:

33797

show subpopulations

Gnomad4 AFR

AF:

0.0289

Gnomad4 AMR

AF:

0.00407

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00393

Alfa

AF:

0.00423

Hom.:

Bravo

AF:

0.0102

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 25, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 29, 2016

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

Aug 09, 2017

- -

Allan-Herndon-Dudley syndrome

Other:1

not provided, no classification provided

literature only

GeneReviews

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

9.8

DANN

Benign

0.73

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