X-74421416-A-G

Variant names:

• chrX-74421416-A-G
• rs201853949
• NM_006517.5:c.-222A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006517.5(SLC16A2):​c.-222A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. 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: 11)
  • Exomes 𝑓: 0.0000027 (0 hom. 0 hem.)
• Consequence: SLC16A2 NM_006517.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.916
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.021).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC16A2	NM_006517.5	c.-222A>G		upstream_gene_variant		ENST00000587091.6	NP_006508.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC16A2	ENST00000587091.6	c.-222A>G		upstream_gene_variant		1	NM_006517.5	ENSP00000465734.1

Frequencies

GnomAD3 genomes Cov.: 11

GnomAD4 exome AF: 0.00000266 AC: 1 AN: 375439 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 129769

African (AFR) AF: 0.00 AC: 0 AN: 11913

American (AMR) AF: 0.00 AC: 0 AN: 26030

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13123

East Asian (EAS) AF: 0.00 AC: 0 AN: 22133

South Asian (SAS) AF: 0.00 AC: 0 AN: 34435

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1844

European-Non Finnish (NFE) AF: 0.00000463 AC: 1 AN: 215788

Other (OTH) AF: 0.00 AC: 0 AN: 21643

GnomAD4 genome Cov.: 11

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	17
DANN	Benign	0.93
PhyloP100		0.92
PromoterAI		0.67	Over-expression

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs201853949; hg19: chrX-73641251;