rs113994164

chrX-74529316-GCTT-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM1 PM4_Supporting

The NM_006517.5(SLC16A2):c.1279_1281del(p.Phe427del) variant causes a inframe deletion change. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 23)
• Consequence: SLC16A2 NM_006517.5 inframe_deletion
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 5.95

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 Uncertain_significance. Variant got 3 ACMG points.

• PM1: In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 2 uncertain in NM_006517.5
• PM4: Nonframeshift variant in NON repetitive region in NM_006517.5. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC16A2	NM_006517.5	c.1279_1281del	p.Phe427del	inframe_deletion	5/6	ENST00000587091.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC16A2	ENST00000587091.6	c.1279_1281del	p.Phe427del	inframe_deletion	5/6	1	NM_006517.5	P1
SLC16A2	ENST00000590447.1	c.611-2012_611-2010del		intron_variant		5
SLC16A2	ENST00000636771.1	c.*980_*982del		3_prime_UTR_variant, NMD_transcript_variant	6/7	5

Frequencies

GnomAD3 genomes Cov.: 23

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

GnomAD4 genome Cov.: 23

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Allan-Herndon-Dudley syndrome Other:1

not provided, no classification provided

literature only

GeneReviews

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Computational scores

Source: dbNSFP v4.3

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: rs113994164; hg19: chrX-73749151;