rs9050

Variant names:

• chr1-152106838-C-A
• rs9050
• NM_007113.4:c.*547G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007113.4(TCHH):​c.*547G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0437 in 152,262 control chromosomes in the GnomAD database, including 198 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.044 (198 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TCHH NM_007113.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350
• Publications: 13 publications found

Genes affected

TCHH (HGNC:11791): (trichohyalin) The protein encoded by this gene forms crosslinked complexes with itself and keratin intermediate filaments to provide mechanical strength to the hair follicle inner root sheath. The encoded protein also is important for structural integrity of the filiform papillae of the tongue. Defects in this gene are a cause of uncombable hair syndrome. [provided by RefSeq, Feb 2017]

TCHH Gene-Disease associations (from GenCC):

• uncombable hair syndrome 3

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.066 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCHH	NM_007113.4	c.*547G>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000614923.2	NP_009044.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCHH	ENST00000614923.2	c.*547G>T		3_prime_UTR_variant	Exon 3 of 3	5	NM_007113.4	ENSP00000480484.1

Frequencies

GnomAD3 genomes AF: 0.0438 AC: 6659 AN: 152144 Hom.: 198 Cov.: 33

Gnomad AFR AF: 0.0121

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.0369

Gnomad ASJ AF: 0.0769

Gnomad EAS AF: 0.0277

Gnomad SAS AF: 0.0450

Gnomad FIN AF: 0.0199

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0676

Gnomad OTH AF: 0.0478

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 84 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 38

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 74

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0437 AC: 6652 AN: 152262 Hom.: 198 Cov.: 33 AF XY: 0.0414 AC XY: 3079 AN XY: 74444

African (AFR) AF: 0.0121 AC: 501 AN: 41542

American (AMR) AF: 0.0368 AC: 563 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0769 AC: 267 AN: 3472

East Asian (EAS) AF: 0.0278 AC: 144 AN: 5182

South Asian (SAS) AF: 0.0444 AC: 214 AN: 4820

European-Finnish (FIN) AF: 0.0199 AC: 211 AN: 10614

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0676 AC: 4599 AN: 68020

Other (OTH) AF: 0.0473 AC: 100 AN: 2114

Alfa AF: 0.0628 Hom.: 338

Bravo AF: 0.0440

Asia WGS AF: 0.0320 AC: 111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.23
DANN	Benign	0.50
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

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: rs9050; hg19: chr1-152079314;