SLC16A2 p.Asp521Glu

Variant names:

• chrX-74531496-C-A
• NM_006517.5:c.1563C>A
• SLC16A2 p.Asp521Glu

Your query was ambiguous. Multiple possible variants found:

• chrX-74531496-C-A
• chrX-74531496-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006517.5(SLC16A2):​c.1563C>A​(p.Asp521Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: SLC16A2 NM_006517.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274
• 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, PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03726828).

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.1563C>A	p.Asp521Glu	missense	Exon 6 of 6	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.1563C>A	p.Asp521Glu	missense	Exon 6 of 6	ENSP00000465734.1	P36021
	SLC16A2	ENST00000878592.1		c.1677C>A	p.Asp559Glu	missense	Exon 7 of 7	ENSP00000548651.1
	SLC16A2	ENST00000922847.1		c.1641C>A	p.Asp547Glu	missense	Exon 7 of 7	ENSP00000592906.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-1.2
CADD	Benign	0.045
DANN	Benign	0.75
DEOGEN2	Benign	0.11	T
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.60	N
PhyloP100		-0.27
PrimateAI	Benign	0.40	T
Sift4G	Benign	0.82	T
Varity_R		0.060
gMVP		0.064
Mutation Taster		=90/10	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-73751331;