rs17680262

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-109916731-C-A
• chr12-109916731-C-G
• chr12-109916731-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000537880.1(TCHP):​n.1482C>A 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 0.00000226 in 884,054 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: 33)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: TCHP ENST00000537880.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.21
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000226 AC: 2 AN: 884054 Hom.: 0 Cov.: 11 AF XY: 0.00000438 AC XY: 2 AN XY: 456426

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 20606

American (AMR) AF: 0.00 AC: 0 AN: 28830

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18984

East Asian (EAS) AF: 0.00 AC: 0 AN: 35456

South Asian (SAS) AF: 0.0000319 AC: 2 AN: 62732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4484

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 626718

Other (OTH) AF: 0.00 AC: 0 AN: 40946

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.035
DANN	Benign	0.39
PhyloP100		-3.2

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

Other links and lift over

dbSNP: rs17680262; hg19: chr12-110354536;