NM_001008536.2:c.2533G>T

Variant names:

• chr1-152085149-C-A
• rs778208087
• NM_001008536.2:c.2533G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001008536.2(TCHHL1):​c.2533G>T​(p.Asp845Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D845H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TCHHL1 NM_001008536.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.631

Genes affected

TCHHL1 (HGNC:31796): (trichohyalin like 1) This gene belongs to the S100 fused-type protein (SFTP) gene family, and is located in a cluster of SFTP genes on chromosome 1q21. Several members of this family have been implicated in the development of complex skin disorders. This gene is evolutionarily conserved; its expression appears to be hair-specific and spatially restricted within the distal inner root sheath of the hair follicle. It thus may have an important role in hair morphogenesis. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19297656).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCHHL1	NM_001008536.2	c.2533G>T	p.Asp845Tyr	missense_variant	Exon 3 of 3	ENST00000368806.2	NP_001008536.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCHHL1	ENST00000368806.2	c.2533G>T	p.Asp845Tyr	missense_variant	Exon 3 of 3	1	NM_001008536.2	ENSP00000357796.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.18
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.36
MutPred		0.53		Gain of sheet (P = 0.0049);
MVP		0.22
MPC		0.15
ClinPred		0.85	D
GERP RS		3.0
Varity_R		0.13
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs778208087; hg19: chr1-152057625;