chrX-74448994-C-T

Variant names:

• chrX-74448994-C-T
• rs479640
• NM_006517.5:c.430+26927C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006517.5(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 NM_006517.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.768
• Publications: 6 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -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.

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.430+26927C>T		intron	N/A	NP_006508.2	P36021

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A2	ENST00000587091.6	TSL:1 MANE Select	c.430+26927C>T		intron	N/A	ENSP00000465734.1	P36021
	SLC16A2	ENST00000878592.1		c.430+26927C>T		intron	N/A	ENSP00000548651.1
	SLC16A2	ENST00000922847.1		c.431-3762C>T		intron	N/A	ENSP00000592906.1

Frequencies

GnomAD3 genomes AF: 0.451 AC: 49786 AN: 110306 Hom.: 9056 Cov.: 23

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

African (AFR) AF: 0.630 AC: 19073 AN: 30277

American (AMR) AF: 0.513 AC: 5291 AN: 10312

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 817 AN: 2633

East Asian (EAS) AF: 0.965 AC: 3382 AN: 3503

South Asian (SAS) AF: 0.605 AC: 1558 AN: 2577

European-Finnish (FIN) AF: 0.364 AC: 2134 AN: 5868

Middle Eastern (MID) AF: 0.383 AC: 80 AN: 209

European-Non Finnish (NFE) AF: 0.316 AC: 16702 AN: 52788

Other (OTH) AF: 0.441 AC: 671 AN: 1520

Alfa AF: 0.387 Hom.: 13845

Bravo AF: 0.475

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.98
DANN	Benign	0.63
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs479640; hg19: chrX-73668829;