1-152110849-A-T

Position:

• chr1-152110849-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007113.4(TCHH):​c.2368T>A​(p.Leu790Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,608,706 control chromosomes in the GnomAD database, including 26,853 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.14 (2128 hom., cov: 32)
  • Exomes 𝑓: 0.17 (24725 hom.)
• Consequence: TCHH NM_007113.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600

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 (MetaRNN=0.0053429008).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCHH	NM_007113.4	c.2368T>A	p.Leu790Met	missense_variant	3/3	ENST00000614923.2	NP_009044.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCHH	ENST00000614923.2	c.2368T>A	p.Leu790Met	missense_variant	3/3	5	NM_007113.4	ENSP00000480484.1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21279 AN: 150848 Hom.: 2126 Cov.: 32

Gnomad AFR AF: 0.0339

Gnomad AMI AF: 0.0887

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.00180

Gnomad SAS AF: 0.0857

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.148

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.147

GnomAD3 exomes AF: 0.152 AC: 37102 AN: 244738 Hom.: 3798 AF XY: 0.155 AC XY: 20681 AN XY: 133490

Gnomad AFR exome AF: 0.0266

Gnomad AMR exome AF: 0.0866

Gnomad ASJ exome AF: 0.115

Gnomad EAS exome AF: 0.000557

Gnomad SAS exome AF: 0.0991

Gnomad FIN exome AF: 0.286

Gnomad NFE exome AF: 0.207

Gnomad OTH exome AF: 0.169

GnomAD4 exome AF: 0.174 AC: 254098 AN: 1457738 Hom.: 24725 Cov.: 114 AF XY: 0.174 AC XY: 125990 AN XY: 725418

Gnomad4 AFR exome AF: 0.0279

Gnomad4 AMR exome AF: 0.0877

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.000529

Gnomad4 SAS exome AF: 0.0998

Gnomad4 FIN exome AF: 0.288

Gnomad4 NFE exome AF: 0.192

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.141 AC: 21273 AN: 150968 Hom.: 2128 Cov.: 32 AF XY: 0.142 AC XY: 10480 AN XY: 73788

Gnomad4 AFR AF: 0.0338

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.00181

Gnomad4 SAS AF: 0.0861

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.145

Alfa AF: 0.161 Hom.: 831

Bravo AF: 0.119

TwinsUK AF: 0.191 AC: 709

ALSPAC AF: 0.190 AC: 734

ESP6500AA AF: 0.0360 AC: 145

ESP6500EA AF: 0.178 AC: 1494

ExAC AF: 0.155 AC: 18711

Asia WGS AF: 0.0420 AC: 148 AN: 3478

EpiCase AF: 0.189

EpiControl AF: 0.186

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	14
DANN	Benign	0.51
DEOGEN2	Benign	0.0024	T;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.20	.;T
MetaRNN	Benign	0.0053	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.81	L;L
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.32	N;.
REVEL	Benign	0.032
Sift	Pathogenic	0.0	D;.
Sift4G	Benign	0.23	T;T
Polyphen		0.99	D;D
Vest4		0.052
MPC		0.26
ClinPred		0.0082	T
GERP RS		-0.58
Varity_R		0.10
gMVP		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

Other links and lift over

dbSNP: rs11803731; hg19: chr1-152083325; COSMIC: COSV64274749;