Variant chr1-152107565-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_007113.4(TCHH):c.5652C>G(p.His1884Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TCHH
NM_007113.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.34

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029086143).

BP6

Variant 1-152107565-G-C is Benign according to our data. Variant chr1-152107565-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3324996.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCHH	NM_007113.4 linkuse as main transcript	c.5652C>G	p.His1884Gln	missense_variant	3/3	ENST00000614923.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCHH	ENST00000614923.2 linkuse as main transcript	c.5652C>G	p.His1884Gln	missense_variant	3/3	5	NM_007113.4	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461862

Hom.:

Cov.:

110

AF XY:

0.00000138

AC XY:

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 19, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.016

DANN

Benign

0.38

DEOGEN2

Benign

0.0019

T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0046

LIST_S2

Benign

0.24

.;T

M_CAP

Benign

0.0011

MetaRNN

Benign

0.029

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.7

N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.37

PROVEAN

Benign

0.43

N;.

REVEL

Benign

0.015

Sift

Benign

0.19

T;.

Sift4G

Benign

0.57

T;T

Polyphen

0.0

B;B

Vest4

0.11

MutPred

0.23

Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);

MVP

0.25

MPC

0.38

ClinPred

0.060

GERP RS

-0.077

Varity_R

0.041

gMVP

0.0034

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over