rs746938228

Variant names:

• chrX-74421518-G-A
• rs746938228
• NM_006517.5:c.-120G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_006517.5(SLC16A2):​c.-120G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 968,048 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 22 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000054 (0 hom., 1 hem., cov: 22)
  • Exomes 𝑓: 0.00012 (0 hom. 21 hem.)
• Consequence: SLC16A2 NM_006517.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.834
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.026).
• BP6: Variant X-74421518-G-A is Benign according to our data. Variant chrX-74421518-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 675273.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.000116 (99/856742) while in subpopulation NFE AF = 0.000147 (94/638641). AF 95% confidence interval is 0.000123. There are 0 homozygotes in GnomAdExome4. There are 21 alleles in the male GnomAdExome4 subpopulation. Median coverage is 15. This position passed quality control check.
• BS2: High Hemizygotes in GnomAdExome4 at 21 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.-120G>A		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.-120G>A		5_prime_UTR	Exon 1 of 6	ENSP00000465734.1	P36021
	SLC16A2	ENST00000922847.1		c.-120G>A		5_prime_UTR	Exon 1 of 7	ENSP00000592906.1
	SLC16A2	ENST00000922843.1		c.-120G>A		5_prime_UTR	Exon 1 of 7	ENSP00000592902.1

Frequencies

GnomAD3 genomes AF: 0.0000539 AC: 6 AN: 111306 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000113

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000339 AC: 4 AN: 118094 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000861

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000116 AC: 99 AN: 856742 Hom.: 0 Cov.: 15 AF XY: 0.0000874 AC XY: 21 AN XY: 240266

African (AFR) AF: 0.0000464 AC: 1 AN: 21542

American (AMR) AF: 0.00 AC: 0 AN: 28459

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17408

East Asian (EAS) AF: 0.00 AC: 0 AN: 26927

South Asian (SAS) AF: 0.00 AC: 0 AN: 46275

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3066

European-Non Finnish (NFE) AF: 0.000147 AC: 94 AN: 638641

Other (OTH) AF: 0.000105 AC: 4 AN: 38056

GnomAD4 genome AF: 0.0000539 AC: 6 AN: 111306 Hom.: 0 Cov.: 22 AF XY: 0.0000298 AC XY: 1 AN XY: 33534

African (AFR) AF: 0.00 AC: 0 AN: 30343

American (AMR) AF: 0.00 AC: 0 AN: 10662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2645

East Asian (EAS) AF: 0.00 AC: 0 AN: 3509

South Asian (SAS) AF: 0.00 AC: 0 AN: 2647

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6096

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.000113 AC: 6 AN: 52979

Other (OTH) AF: 0.00 AC: 0 AN: 1503

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000680

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Uncertain	0.99
PhyloP100		0.83
PromoterAI		-0.10	Neutral

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

Other links and lift over

dbSNP: rs746938228; hg19: chrX-73641353;