X-74421585-A-G

Variant names:

• chrX-74421585-A-G
• rs587784385
• NM_006517.5:c.-53A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_006517.5(SLC16A2):​c.-53A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000102 in 1,179,109 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 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 0.0000089 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000010 (0 hom. 6 hem.)
• Consequence: SLC16A2 NM_006517.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.537
• Publications: 0 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: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.072).
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.0000103 (11/1067295) while in subpopulation AFR AF = 0.00027 (7/25898). AF 95% confidence interval is 0.000127. There are 0 homozygotes in GnomAdExome4. There are 6 alleles in the male GnomAdExome4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High Hemizygotes in GnomAdExome4 at 6 XL gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A2	NM_006517.5	MANE Select	c.-53A>G		5_prime_UTR	Exon 1 of 6	NP_006508.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A2	ENST00000587091.6	TSL:1 MANE Select	c.-53A>G		5_prime_UTR	Exon 1 of 6	ENSP00000465734.1

Frequencies

GnomAD3 genomes AF: 0.00000894 AC: 1 AN: 111814 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000325

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000716 AC: 1 AN: 139645 AF XY: 0.0000226

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 11 AN: 1067295 Hom.: 0 Cov.: 29 AF XY: 0.0000175 AC XY: 6 AN XY: 342115

African (AFR) AF: 0.000270 AC: 7 AN: 25898

American (AMR) AF: 0.00 AC: 0 AN: 32987

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19026

East Asian (EAS) AF: 0.00 AC: 0 AN: 29323

South Asian (SAS) AF: 0.0000192 AC: 1 AN: 51996

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34835

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3236

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 824956

Other (OTH) AF: 0.0000666 AC: 3 AN: 45038

GnomAD4 genome AF: 0.00000894 AC: 1 AN: 111814 Hom.: 0 Cov.: 23 AF XY: 0.0000293 AC XY: 1 AN XY: 34078

African (AFR) AF: 0.0000325 AC: 1 AN: 30812

American (AMR) AF: 0.00 AC: 0 AN: 10700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2638

East Asian (EAS) AF: 0.00 AC: 0 AN: 3518

South Asian (SAS) AF: 0.00 AC: 0 AN: 2671

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52879

Other (OTH) AF: 0.00 AC: 0 AN: 1506

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Uncertain	0.99
PhyloP100		0.54
PromoterAI		-0.049	Neutral
Mutation Taster		=82/18	polymorphism

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: rs587784385; hg19: chrX-73641420;