ENST00000922843.1:c.-222A>C – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000922843.1(SLC16A2):c.-222A>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.000051 ( 0 hom., 0 hem., cov: 11)

Exomes 𝑓: 0.000016 ( 0 hom. 1 hem. )

Consequence

SLC16A2
ENST00000922843.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.916

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.023).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000922843.1. 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.-222A>C		upstream_gene	N/A	NP_006508.2	P36021

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC16A2	ENST00000922843.1		c.-222A>C	5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000592902.1
SLC16A2	ENST00000922843.1		c.-222A>C	5_prime_UTR	Exon 1 of 7	ENSP00000592902.1
SLC16A2	ENST00000587091.6	TSL:1 MANE Select	c.-222A>C	upstream_gene	N/A	ENSP00000465734.1	P36021

Frequencies

GnomAD3 genomes

AF:

0.0000507

AC:

AN:

59128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000914

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000112

AC:

AN:

89247

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000304

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000160

AC:

AN:

375437

Hom.:

Cov.:

AF XY:

0.00000771

AC XY:

AN XY:

129767

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

11913

American (AMR)

AF:

0.00

AC:

AN:

26030

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13122

East Asian (EAS)

AF:

0.00

AC:

AN:

22133

South Asian (SAS)

AF:

0.00

AC:

AN:

34435

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28530

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1844

European-Non Finnish (NFE)

AF:

0.0000278

AC:

AN:

215787

Other (OTH)

AF:

0.00

AC:

AN:

21643

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000507

AC:

AN:

59128

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

10232

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

14473

American (AMR)

AF:

0.00

AC:

AN:

4575

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1637

East Asian (EAS)

AF:

0.00

AC:

AN:

1577

South Asian (SAS)

AF:

0.00

AC:

AN:

693

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2073

Middle Eastern (MID)

AF:

0.00

AC:

AN:

126

European-Non Finnish (NFE)

AF:

0.0000914

AC:

AN:

32832

Other (OTH)

AF:

0.00

AC:

AN:

748

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

0.92

PromoterAI

-0.13

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over