Genetic Variant SLC16A2:p.Ser8Ser (chrX-74421661-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_006517.5(SLC16A2):c.24C>T(p.Ser8Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

SLC16A2
NM_006517.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.646

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Allan-Herndon-Dudley syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)

SLC16A2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

BP7

Synonymous conserved (PhyloP=0.646 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006517.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A2	NM_006517.5	MANE Select	c.24C>T	p.Ser8Ser	synonymous	Exon 1 of 6	NP_006508.2	P36021

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC16A2	ENST00000587091.6	TSL:1 MANE Select	c.24C>T	p.Ser8Ser	synonymous	Exon 1 of 6	ENSP00000465734.1	P36021
SLC16A2	ENST00000878592.1		c.24C>T	p.Ser8Ser	synonymous	Exon 1 of 7	ENSP00000548651.1
SLC16A2	ENST00000922847.1		c.24C>T	p.Ser8Ser	synonymous	Exon 1 of 7	ENSP00000592906.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1089332

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

357632

African (AFR)

AF:

0.00

AC:

AN:

26348

American (AMR)

AF:

0.00

AC:

AN:

34614

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19258

East Asian (EAS)

AF:

0.00

AC:

AN:

30027

South Asian (SAS)

AF:

0.00

AC:

AN:

53189

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36547

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3761

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

839752

Other (OTH)

AF:

0.00

AC:

AN:

45836

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

0.65

PromoterAI

0.037

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over