18-75285722-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001308210.2(TSHZ1):c.315C>T(p.Ser105=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,613,672 control chromosomes in the GnomAD database, including 69,953 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (5142 hom., cov: 32)
  • Exomes 𝑓: 0.29 (64811 hom.)
• Consequence: TSHZ1 NM_001308210.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.370

Genes affected

TSHZ1 (HGNC:10669): (teashirt zinc finger homeobox 1) This gene encodes a colon cancer antigen that was defined by serological analysis of recombinant cDNA expression libraries. The encoded protein is a member of the teashirt C2H2-type zinc-finger protein family and may be involved in transcriptional regulation of developmental processes. Mutations in this gene may be associated with congenital aural atresia syndrome. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 18-75285722-C-T is Benign according to our data. Variant chr18-75285722-C-T is described in ClinVar as [Benign]. Clinvar id is 1260276.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-75285722-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.37 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSHZ1	NM_001308210.2	c.315C>T	p.Ser105=	synonymous_variant	2/2	ENST00000580243.3
TSHZ1	NM_005786.6	c.180C>T	p.Ser60=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSHZ1	ENST00000580243.3	c.315C>T	p.Ser105=	synonymous_variant	2/2	2	NM_001308210.2	P1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35861 AN: 151948 Hom.: 5144 Cov.: 32

Gnomad AFR AF: 0.0736

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.244

GnomAD3 exomes AF: 0.263 AC: 65894 AN: 250932 Hom.: 9387 AF XY: 0.266 AC XY: 36146 AN XY: 135636

Gnomad AFR exome AF: 0.0703

Gnomad AMR exome AF: 0.244

Gnomad ASJ exome AF: 0.295

Gnomad EAS exome AF: 0.142

Gnomad SAS exome AF: 0.206

Gnomad FIN exome AF: 0.297

Gnomad NFE exome AF: 0.320

Gnomad OTH exome AF: 0.289

GnomAD4 exome AF: 0.293 AC: 427570 AN: 1461606 Hom.: 64811 Cov.: 38 AF XY: 0.291 AC XY: 211507 AN XY: 727076

Gnomad4 AFR exome AF: 0.0642

Gnomad4 AMR exome AF: 0.253

Gnomad4 ASJ exome AF: 0.299

Gnomad4 EAS exome AF: 0.165

Gnomad4 SAS exome AF: 0.210

Gnomad4 FIN exome AF: 0.299

Gnomad4 NFE exome AF: 0.313

Gnomad4 OTH exome AF: 0.274

GnomAD4 genome AF: 0.236 AC: 35852 AN: 152066 Hom.: 5142 Cov.: 32 AF XY: 0.236 AC XY: 17556 AN XY: 74322

Gnomad4 AFR AF: 0.0734

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.248

Alfa AF: 0.303 Hom.: 18476

Bravo AF: 0.228

Asia WGS AF: 0.195 AC: 679 AN: 3478

EpiCase AF: 0.325

EpiControl AF: 0.327

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 18, 2020

- -

TSHZ1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 15, 2023

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	2.5
Dann	Benign	0.63

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: rs3826609; hg19: chr18-72997677; COSMIC: COSV59007163;