Variant rs201930497 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The NM_007113.4(TCHH):c.991C>T(p.Gln331*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00038 in 1,565,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 24)

Exomes 𝑓: 0.00037 ( 0 hom. )

Consequence

TCHH
NM_007113.4 stop_gained

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 0.534

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 1-152112226-G-A is Pathogenic according to our data. Variant chr1-152112226-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 374835.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-152112226-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCHH	NM_007113.4 linkuse as main transcript	c.991C>T	p.Gln331*	stop_gained	3/3	ENST00000614923.2	NP_009044.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCHH	ENST00000614923.2 linkuse as main transcript	c.991C>T	p.Gln331*	stop_gained	3/3	5	NM_007113.4	ENSP00000480484.1		Q07283

Frequencies

GnomAD3 genomes

AF:

0.000530

AC:

AN:

120818

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000703

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000131

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000858

Gnomad OTH

AF:

0.000613

GnomAD3 exomes

AF:

0.000327

AC:

AN:

238272

Hom.:

AF XY:

0.000299

AC XY:

AN XY:

130304

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000367

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000224

Gnomad NFE exome

AF:

0.000517

Gnomad OTH exome

AF:

0.000858

GnomAD4 exome

AF:

0.000367

AC:

530

AN:

1444114

Hom.:

Cov.:

AF XY:

0.000367

AC XY:

264

AN XY:

718574

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000423

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000107

Gnomad4 NFE exome

AF:

0.000440

Gnomad4 OTH exome

AF:

0.000336

GnomAD4 genome

AF:

0.000529

AC:

AN:

120908

Hom.:

Cov.:

AF XY:

0.000545

AC XY:

AN XY:

58734

show subpopulations

Gnomad4 AFR

AF:

0.000154

Gnomad4 AMR

AF:

0.000703

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000131

Gnomad4 NFE

AF:

0.000858

Gnomad4 OTH

AF:

0.000609

Alfa

AF:

0.000274

Hom.:

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000243

AC:

ESP6500EA

AF:

0.000600

AC:

ExAC

AF:

0.000356

AC:

EpiCase

AF:

0.000656

EpiControl

AF:

0.000358

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Uncombable hair syndrome 3

Pathogenic:2

Likely pathogenic, criteria provided, single submitter	clinical testing	Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota	Mar 27, 2018	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Aug 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.060

BayesDel_noAF

Uncertain

0.030

CADD

Uncertain

DANN

Uncertain

0.98

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.032

Vest4

0.10

GERP RS

-0.013

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over