chr12-109916731-C-T

Variant names:

• chr12-109916731-C-T
• rs17680262
• ENST00000537880.1:n.1482C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000537880.1(TCHP):​n.1482C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0754 in 1,035,628 control chromosomes in the GnomAD database, including 3,585 homozygotes. 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: 𝑓 0.055 (328 hom., cov: 33)
  • Exomes 𝑓: 0.079 (3257 hom.)
• Consequence: TCHP ENST00000537880.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.21
• Publications: 13 publications found

Genes affected

TCHP (HGNC:28135): (trichoplein keratin filament binding) Involved in apoptotic process; negative regulation of cell growth; and negative regulation of cilium assembly. Located in several cellular components, including apical cortex; cytoskeleton; and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCHP	NM_001143852.2	c.*108C>T		3_prime_UTR_variant	Exon 13 of 13	ENST00000405876.9	NP_001137324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCHP	ENST00000405876.9	c.*108C>T		3_prime_UTR_variant	Exon 13 of 13	1	NM_001143852.2	ENSP00000384520.4

Frequencies

GnomAD3 genomes AF: 0.0553 AC: 8422 AN: 152188 Hom.: 328 Cov.: 33

Gnomad AFR AF: 0.0163

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0446

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.0732

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0871

Gnomad OTH AF: 0.0530

GnomAD4 exome AF: 0.0789 AC: 69715 AN: 883322 Hom.: 3257 Cov.: 11 AF XY: 0.0765 AC XY: 34903 AN XY: 456056

African (AFR) AF: 0.0126 AC: 259 AN: 20606

American (AMR) AF: 0.0294 AC: 848 AN: 28818

Ashkenazi Jewish (ASJ) AF: 0.0422 AC: 801 AN: 18978

East Asian (EAS) AF: 0.000169 AC: 6 AN: 35456

South Asian (SAS) AF: 0.0197 AC: 1238 AN: 62724

European-Finnish (FIN) AF: 0.0824 AC: 3729 AN: 45276

Middle Eastern (MID) AF: 0.0234 AC: 105 AN: 4484

European-Non Finnish (NFE) AF: 0.0959 AC: 60010 AN: 626066

Other (OTH) AF: 0.0665 AC: 2719 AN: 40914

GnomAD4 genome AF: 0.0553 AC: 8419 AN: 152306 Hom.: 328 Cov.: 33 AF XY: 0.0532 AC XY: 3961 AN XY: 74472

African (AFR) AF: 0.0163 AC: 676 AN: 41578

American (AMR) AF: 0.0445 AC: 681 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0323 AC: 112 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.0168 AC: 81 AN: 4830

European-Finnish (FIN) AF: 0.0732 AC: 777 AN: 10614

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0870 AC: 5919 AN: 68004

Other (OTH) AF: 0.0520 AC: 110 AN: 2116

Alfa AF: 0.0737 Hom.: 794

Bravo AF: 0.0507

Asia WGS AF: 0.00838 AC: 29 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.092
DANN	Benign	0.39
PhyloP100		-3.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs17680262; hg19: chr12-110354536;