chr1-152110849-A-G

Variant names:

• chr1-152110849-A-G
• rs11803731
• NM_007113.4:c.2368T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_007113.4(TCHH):​c.2368T>C​(p.Leu790Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,782 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TCHH NM_007113.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600
• Publications: 47 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=0.006 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCHH	NM_007113.4	c.2368T>C	p.Leu790Leu	synonymous_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.2368T>C	p.Leu790Leu	synonymous_variant	Exon 3 of 3	5	NM_007113.4	ENSP00000480484.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457782 Hom.: 0 Cov.: 114 AF XY: 0.00000138 AC XY: 1 AN XY: 725440

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111872

Other (OTH) AF: 0.0000166 AC: 1 AN: 60356

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 831

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.8
DANN	Benign	0.36
PhyloP100		0.0060
Mutation Taster		=100/0	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: rs11803731; hg19: chr1-152083325;