X-74448994-C-T

Position:

• chrX-74448994-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000587091.6(SLC16A2):​c.430+26927C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 110,361 control chromosomes in the GnomAD database, including 9,068 homozygotes. There are 14,795 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: 𝑓 0.45 (9068 hom., 14795 hem., cov: 23)
• Consequence: SLC16A2 ENST00000587091.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.768

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC16A2	NM_006517.5	c.430+26927C>T		intron_variant		ENST00000587091.6	NP_006508.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC16A2	ENST00000587091.6	c.430+26927C>T		intron_variant		1	NM_006517.5	ENSP00000465734	P1
SLC16A2	ENST00000636771.1	c.176+26927C>T		intron_variant, NMD_transcript_variant		5		ENSP00000490445

Frequencies

GnomAD3 genomes AF: 0.451 AC: 49786 AN: 110306 Hom.: 9056 Cov.: 23 AF XY: 0.452 AC XY: 14746 AN XY: 32602

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.433

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.452 AC: 49849 AN: 110361 Hom.: 9068 Cov.: 23 AF XY: 0.453 AC XY: 14795 AN XY: 32667

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.965

Gnomad4 SAS AF: 0.605

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.441

Alfa AF: 0.373 Hom.: 8871

Bravo AF: 0.475

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.98
DANN	Benign	0.63

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: rs479640; hg19: chrX-73668829;