rs9050

chr1-152106838-C-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TCHH	NM_007113.4	c.*547G>T		3_prime_UTR_variant	3/3	ENST00000614923.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCHH	ENST00000614923.2	c.*547G>T		3_prime_UTR_variant	3/3	5	NM_007113.4	P1

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

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.0121

Gnomad4 AMR AF: 0.0368

Gnomad4 ASJ AF: 0.0769

Gnomad4 EAS AF: 0.0278

Gnomad4 SAS AF: 0.0444

Gnomad4 FIN AF: 0.0199

Gnomad4 NFE AF: 0.0676

Gnomad4 OTH AF: 0.0473

Alfa AF: 0.0634 Hom.: 198

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

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: rs9050; hg19: chr1-152079314;