rs200444038

Positions:

• chrX-74521006-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_006517.5(SLC16A2):​c.447C>T​(p.Leu149=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000864 in 1,209,865 control chromosomes in the GnomAD database, including 3 homozygotes. There are 326 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00065 (1 hom., 24 hem., cov: 23)
  • Exomes 𝑓: 0.00089 (2 hom. 302 hem.)
• Consequence: SLC16A2 NM_006517.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.814

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 Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant X-74521006-C-T is Benign according to our data. Variant chrX-74521006-C-T is described in ClinVar as [Benign]. Clinvar id is 436734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.814 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000653 (73/111795) while in subpopulation NFE AF= 0.000884 (47/53179). AF 95% confidence interval is 0.000682. There are 1 homozygotes in gnomad4. There are 24 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd4 at 24 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC16A2	NM_006517.5	c.447C>T	p.Leu149=	synonymous_variant	2/6	ENST00000587091.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC16A2	ENST00000587091.6	c.447C>T	p.Leu149=	synonymous_variant	2/6	1	NM_006517.5	P1
SLC16A2	ENST00000636771.1	c.*148C>T		3_prime_UTR_variant, NMD_transcript_variant	3/7	5

Frequencies

GnomAD3 genomes AF: 0.000653 AC: 73 AN: 111795 Hom.: 1 Cov.: 23 AF XY: 0.000707 AC XY: 24 AN XY: 33961

Gnomad AFR AF: 0.000261

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00416

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000994

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000884

Gnomad OTH AF: 0.000667

GnomAD3 exomes AF: 0.000698 AC: 128 AN: 183408 Hom.: 1 AF XY: 0.000649 AC XY: 44 AN XY: 67846

Gnomad AFR exome AF: 0.000152

Gnomad AMR exome AF: 0.000146

Gnomad ASJ exome AF: 0.00334

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00137

Gnomad NFE exome AF: 0.000904

Gnomad OTH exome AF: 0.000221

GnomAD4 exome AF: 0.000885 AC: 972 AN: 1098070 Hom.: 2 Cov.: 31 AF XY: 0.000831 AC XY: 302 AN XY: 363424

Gnomad4 AFR exome AF: 0.000189

Gnomad4 AMR exome AF: 0.0000852

Gnomad4 ASJ exome AF: 0.00284

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00205

Gnomad4 NFE exome AF: 0.000947

Gnomad4 OTH exome AF: 0.000629

GnomAD4 genome AF: 0.000653 AC: 73 AN: 111795 Hom.: 1 Cov.: 23 AF XY: 0.000707 AC XY: 24 AN XY: 33961

Gnomad4 AFR AF: 0.000261

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00416

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000994

Gnomad4 NFE AF: 0.000884

Gnomad4 OTH AF: 0.000667

Alfa AF: 0.00178 Hom.: 16

Bravo AF: 0.000601

EpiCase AF: 0.000382

EpiControl AF: 0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 14, 2017

- -

Spastic paraplegia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 09, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	0.091
DANN	Benign	0.74

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: rs200444038; hg19: chrX-73740841;