Variant rs200444038 details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.814

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 -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	Protein	UniProt
SLC16A2	NM_006517.5 linkuse as main transcript	c.447C>T	p.Leu149=	synonymous_variant	2/6	ENST00000587091.6	NP_006508.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC16A2	ENST00000587091.6 linkuse as main transcript	c.447C>T	p.Leu149=	synonymous_variant	2/6	1	NM_006517.5	ENSP00000465734	P1
SLC16A2	ENST00000636771.1 linkuse as main transcript	c.*148C>T		3_prime_UTR_variant, NMD_transcript_variant	3/7	5		ENSP00000490445

Frequencies

GnomAD3 genomes

AF:

0.000653

AC:

AN:

111795

Hom.:

Cov.:

AF XY:

0.000707

AC XY:

AN XY:

33961

show subpopulations

Gnomad AFR

AF:

0.000261

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00416

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000994

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000884

Gnomad OTH

AF:

0.000667

GnomAD3 exomes

AF:

0.000698

AC:

128

AN:

183408

Hom.:

AF XY:

0.000649

AC XY:

AN XY:

67846

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.000146

Gnomad ASJ exome

AF:

0.00334

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00137

Gnomad NFE exome

AF:

0.000904

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000885

AC:

972

AN:

1098070

Hom.:

Cov.:

AF XY:

0.000831

AC XY:

302

AN XY:

363424

show subpopulations

Gnomad4 AFR exome

AF:

0.000189

Gnomad4 AMR exome

AF:

0.0000852

Gnomad4 ASJ exome

AF:

0.00284

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00205

Gnomad4 NFE exome

AF:

0.000947

Gnomad4 OTH exome

AF:

0.000629

GnomAD4 genome

AF:

0.000653

AC:

AN:

111795

Hom.:

Cov.:

AF XY:

0.000707

AC XY:

AN XY:

33961

show subpopulations

Gnomad4 AFR

AF:

0.000261

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00416

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000994

Gnomad4 NFE

AF:

0.000884

Gnomad4 OTH

AF:

0.000667

Alfa

AF:

0.00178

Hom.:

Bravo

AF:

0.000601

EpiCase

AF:

0.000382

EpiControl

AF:

0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

Labcorp Genetics (formerly Invitae), Labcorp

Dec 09, 2023

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

0.091

DANN

Benign

0.74

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