rs797045964

Positions:

• chrX-74421876-C-G
• chrX-74421876-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_006517.5(SLC16A2):​c.239C>G​(p.Thr80Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000457 in 1,095,211 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. 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: 24)
  • Exomes 𝑓: 0.0000046 (0 hom. 2 hem.)
• Consequence: SLC16A2 NM_006517.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08797175).
• BS2: High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC16A2	NM_006517.5	c.239C>G	p.Thr80Arg	missense_variant	1/6	ENST00000587091.6	NP_006508.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC16A2	ENST00000587091.6	c.239C>G	p.Thr80Arg	missense_variant	1/6	1	NM_006517.5	ENSP00000465734	P1
SLC16A2	ENST00000636771.1			upstream_gene_variant		5		ENSP00000490445

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD3 exomes AF: 0.00000586 AC: 1 AN: 170705 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 60345

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000134

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000457 AC: 5 AN: 1095211 Hom.: 0 Cov.: 32 AF XY: 0.00000554 AC XY: 2 AN XY: 361285

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000595

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.69	T
M_CAP	Pathogenic	0.50	D
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	0.97	N;N
PrimateAI	Uncertain	0.63	T
Sift4G	Benign	0.50	T
Polyphen		0.013	B
Vest4		0.12
MutPred		0.20		Loss of glycosylation at T80 (P = 7e-04);
MVP		0.22
MPC		1.1
ClinPred		0.070	T
GERP RS		3.1
Varity_R		0.18
gMVP		0.21

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

Other links and lift over

dbSNP: rs797045964; hg19: chrX-73641711;