NM_006517.5:c.-102_-97dupGGCAGC

Variant names:

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

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_-97dupGGCAGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 984,326 control chromosomes in the GnomAD database, including 46 homozygotes. There are 478 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (24 hom., 260 hem., cov: 22)
  • Exomes 𝑓: 0.0012 (22 hom. 218 hem.)
• Consequence: SLC16A2 NM_006517.5 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.19
• 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-A-AGGCAGC is Benign according to our data. Variant chrX-74421523-A-AGGCAGC is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 587847.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0105 (1167/111225) while in subpopulation AFR AF = 0.0364 (1111/30521). AF 95% confidence interval is 0.0346. There are 24 homozygotes in GnomAd4. There are 260 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 24 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_-97dupGGCAGC		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_-97dupGGCAGC		5_prime_UTR	Exon 1 of 6	ENSP00000465734.1	P36021
	SLC16A2	ENST00000878592.1		c.-102_-97dupGGCAGC		5_prime_UTR	Exon 1 of 7	ENSP00000548651.1
	SLC16A2	ENST00000922847.1		c.-102_-97dupGGCAGC		5_prime_UTR	Exon 1 of 7	ENSP00000592906.1

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1163 AN: 111179 Hom.: 24 Cov.: 22

Gnomad AFR AF: 0.0363

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00404

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00418

Gnomad NFE AF: 0.0000568

Gnomad OTH AF: 0.00602

GnomAD2 exomes AF: 0.00249 AC: 296 AN: 118869 AF XY: 0.00147

Gnomad AFR exome AF: 0.0353

Gnomad AMR exome AF: 0.000786

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000170

Gnomad OTH exome AF: 0.00118

GnomAD4 exome AF: 0.00117 AC: 1020 AN: 873101 Hom.: 22 Cov.: 16 AF XY: 0.000894 AC XY: 218 AN XY: 243865

African (AFR) AF: 0.0389 AC: 844 AN: 21714

American (AMR) AF: 0.00143 AC: 41 AN: 28614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17561

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

South Asian (SAS) AF: 0.000107 AC: 5 AN: 46670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36025

Middle Eastern (MID) AF: 0.000972 AC: 3 AN: 3086

European-Non Finnish (NFE) AF: 0.0000275 AC: 18 AN: 653783

Other (OTH) AF: 0.00283 AC: 109 AN: 38573

GnomAD4 genome AF: 0.0105 AC: 1167 AN: 111225 Hom.: 24 Cov.: 22 AF XY: 0.00776 AC XY: 260 AN XY: 33507

African (AFR) AF: 0.0364 AC: 1111 AN: 30521

American (AMR) AF: 0.00403 AC: 43 AN: 10659

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2635

East Asian (EAS) AF: 0.00 AC: 0 AN: 3468

South Asian (SAS) AF: 0.00 AC: 0 AN: 2606

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

Middle Eastern (MID) AF: 0.00459 AC: 1 AN: 218

European-Non Finnish (NFE) AF: 0.0000568 AC: 3 AN: 52855

Other (OTH) AF: 0.00594 AC: 9 AN: 1515

Alfa AF: 0.000482 Hom.: 2

Asia WGS AF: 0.00120 AC: 3 AN: 2520

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Allan-Herndon-Dudley syndrome (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=77/23	polymorphism (auto)

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;