NM_006517.5:c.-124T>C

Variant names:

• chrX-74421514-T-C
• rs771114990
• NM_006517.5:c.-124T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006517.5(SLC16A2):​c.-124T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000212 in 949,483 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 60 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 0.000073 (0 hom., 2 hem., cov: 23)
  • Exomes 𝑓: 0.00023 (0 hom. 58 hem.)
• Consequence: SLC16A2 NM_006517.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0860
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant X-74421514-T-C is Benign according to our data. Variant chrX-74421514-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1768902.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.00023 (193/839411) while in subpopulation EAS AF = 0.000411 (11/26786). AF 95% confidence interval is 0.000233. There are 0 homozygotes in GnomAdExome4. There are 58 alleles in the male GnomAdExome4 subpopulation. Median coverage is 15. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 2 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.-124T>C		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.-124T>C		5_prime_UTR	Exon 1 of 6	ENSP00000465734.1	P36021
	SLC16A2	ENST00000922847.1		c.-124T>C		5_prime_UTR	Exon 1 of 7	ENSP00000592906.1
	SLC16A2	ENST00000922843.1		c.-124T>C		5_prime_UTR	Exon 1 of 7	ENSP00000592902.1

Frequencies

GnomAD3 genomes AF: 0.0000727 AC: 8 AN: 110032 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000949

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: 0.000114

Gnomad OTH AF: 0.000672

GnomAD2 exomes AF: 0.000179 AC: 21 AN: 117157 AF XY: 0.000132

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000199

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000550

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000240

Gnomad OTH exome AF: 0.000298

GnomAD4 exome AF: 0.000230 AC: 193 AN: 839411 Hom.: 0 Cov.: 15 AF XY: 0.000246 AC XY: 58 AN XY: 236249

African (AFR) AF: 0.00 AC: 0 AN: 20924

American (AMR) AF: 0.000212 AC: 6 AN: 28286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17309

East Asian (EAS) AF: 0.000411 AC: 11 AN: 26786

South Asian (SAS) AF: 0.00 AC: 0 AN: 46011

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3019

European-Non Finnish (NFE) AF: 0.000266 AC: 166 AN: 623231

Other (OTH) AF: 0.000267 AC: 10 AN: 37497

GnomAD4 genome AF: 0.0000727 AC: 8 AN: 110072 Hom.: 0 Cov.: 23 AF XY: 0.0000614 AC XY: 2 AN XY: 32598

African (AFR) AF: 0.00 AC: 0 AN: 29962

American (AMR) AF: 0.0000948 AC: 1 AN: 10549

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2626

East Asian (EAS) AF: 0.00 AC: 0 AN: 3429

South Asian (SAS) AF: 0.00 AC: 0 AN: 2573

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5926

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.000114 AC: 6 AN: 52603

Other (OTH) AF: 0.000663 AC: 1 AN: 1508

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.0000869

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Benign	0.62
PhyloP100		-0.086
PromoterAI		-0.0046	Neutral
Mutation Taster		=300/0	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

Other links and lift over

dbSNP: rs771114990; hg19: chrX-73641349;