X-74456451-A-G

Variant names:

• chrX-74456451-A-G
• rs496549
• NM_006517.5:c.430+34384A>G

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+34384A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 110,193 control chromosomes in the GnomAD database, including 8,597 homozygotes. There are 14,299 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 0.44 (8597 hom., 14299 hem., cov: 22)
• Consequence: SLC16A2 NM_006517.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.976
• Publications: 4 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.937 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+34384A>G		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+34384A>G		intron	N/A	ENSP00000465734.1	P36021
	SLC16A2	ENST00000878592.1		c.430+34384A>G		intron	N/A	ENSP00000548651.1
	SLC16A2	ENST00000922847.1		c.508+3618A>G		intron	N/A	ENSP00000592906.1

Frequencies

GnomAD3 genomes AF: 0.441 AC: 48522 AN: 110144 Hom.: 8587 Cov.: 22

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.372

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.441 AC: 48583 AN: 110193 Hom.: 8597 Cov.: 22 AF XY: 0.440 AC XY: 14299 AN XY: 32493

African (AFR) AF: 0.597 AC: 18052 AN: 30225

American (AMR) AF: 0.507 AC: 5234 AN: 10317

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 812 AN: 2626

East Asian (EAS) AF: 0.965 AC: 3342 AN: 3464

South Asian (SAS) AF: 0.603 AC: 1551 AN: 2571

European-Finnish (FIN) AF: 0.351 AC: 2031 AN: 5788

Middle Eastern (MID) AF: 0.374 AC: 80 AN: 214

European-Non Finnish (NFE) AF: 0.316 AC: 16674 AN: 52792

Other (OTH) AF: 0.437 AC: 664 AN: 1521

Alfa AF: 0.380 Hom.: 12949

Bravo AF: 0.464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.29
DANN	Benign	0.62
PhyloP100		-0.98
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: rs496549; hg19: chrX-73676286;