X-74421523-AGGCAGC-A

Variant names:

• chrX-74421523-AGGCAGC-A
• rs760787234
• NM_006517.5:c.-102_-97delGGCAGC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_006517.5(SLC16A2):​c.-102_-97delGGCAGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000233 in 984,303 control chromosomes in the GnomAD database, including 1 homozygotes. There are 61 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., 3 hem., cov: 22)
  • Exomes 𝑓: 0.00025 (1 hom. 58 hem.)
• Consequence: SLC16A2 NM_006517.5 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.94
• 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: ClinGen, G2P, PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant X-74421523-AGGCAGC-A is Benign according to our data. Variant chrX-74421523-AGGCAGC-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 193344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.000245 (214/873103) while in subpopulation NFE AF = 0.000231 (151/653781). AF 95% confidence interval is 0.000201. There are 1 homozygotes in GnomAdExome4. There are 58 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 3 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A2	NM_006517.5	MANE Select	c.-102_-97delGGCAGC		5_prime_UTR	Exon 1 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.-102_-97delGGCAGC		5_prime_UTR	Exon 1 of 6	ENSP00000465734.1	P36021
	SLC16A2	ENST00000878592.1		c.-102_-97delGGCAGC		5_prime_UTR	Exon 1 of 7	ENSP00000548651.1
	SLC16A2	ENST00000922847.1		c.-102_-97delGGCAGC		5_prime_UTR	Exon 1 of 7	ENSP00000592906.1

Frequencies

GnomAD3 genomes AF: 0.000135 AC: 15 AN: 111200 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000939

Gnomad ASJ AF: 0.00190

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000170

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000278 AC: 33 AN: 118869 AF XY: 0.000184

Gnomad AFR exome AF: 0.000132

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00302

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000234

Gnomad OTH exome AF: 0.000591

GnomAD4 exome AF: 0.000245 AC: 214 AN: 873103 Hom.: 1 AF XY: 0.000238 AC XY: 58 AN XY: 243865

African (AFR) AF: 0.0000460 AC: 1 AN: 21721

American (AMR) AF: 0.00 AC: 0 AN: 28614

Ashkenazi Jewish (ASJ) AF: 0.00296 AC: 52 AN: 17560

East Asian (EAS) AF: 0.00 AC: 0 AN: 27075

South Asian (SAS) AF: 0.0000214 AC: 1 AN: 46670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36023

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3086

European-Non Finnish (NFE) AF: 0.000231 AC: 151 AN: 653781

Other (OTH) AF: 0.000233 AC: 9 AN: 38573

GnomAD4 genome AF: 0.000135 AC: 15 AN: 111200 Hom.: 0 Cov.: 22 AF XY: 0.0000896 AC XY: 3 AN XY: 33464

African (AFR) AF: 0.00 AC: 0 AN: 30481

American (AMR) AF: 0.0000939 AC: 1 AN: 10646

Ashkenazi Jewish (ASJ) AF: 0.00190 AC: 5 AN: 2635

East Asian (EAS) AF: 0.00 AC: 0 AN: 3479

South Asian (SAS) AF: 0.00 AC: 0 AN: 2615

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6064

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.000170 AC: 9 AN: 52862

Other (OTH) AF: 0.00 AC: 0 AN: 1495

Alfa AF: 0.000482 Hom.: 2

Bravo AF: 0.000189

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9
Mutation Taster		=281/19	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs760787234; hg19: chrX-73641358;