rs3809997

chr18-75286931-T-C

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.1524T>C(p.Pro508=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,613,950 control chromosomes in the GnomAD database, including 125,877 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (11732 hom., cov: 33)
  • Exomes 𝑓: 0.39 (114145 hom.)
• Consequence: TSHZ1 NM_001308210.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.29

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=-0.91).
• BP6: Variant 18-75286931-T-C is Benign according to our data. Variant chr18-75286931-T-C is described in ClinVar as [Benign]. Clinvar id is 327819.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-75286931-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-3.29 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSHZ1	NM_001308210.2	c.1524T>C	p.Pro508=	synonymous_variant	2/2	ENST00000580243.3
TSHZ1	NM_005786.6	c.1389T>C	p.Pro463=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSHZ1	ENST00000580243.3	c.1524T>C	p.Pro508=	synonymous_variant	2/2	2	NM_001308210.2	P1
TSHZ1	ENST00000322038.5	c.1389T>C	p.Pro463=	synonymous_variant	2/2	1
TSHZ1	ENST00000584217.1	n.4068T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59146 AN: 151978 Hom.: 11725 Cov.: 33

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.398

GnomAD3 exomes AF: 0.369 AC: 92604 AN: 250962 Hom.: 17842 AF XY: 0.374 AC XY: 50841 AN XY: 135770

Gnomad AFR exome AF: 0.390

Gnomad AMR exome AF: 0.296

Gnomad ASJ exome AF: 0.404

Gnomad EAS exome AF: 0.158

Gnomad SAS exome AF: 0.387

Gnomad FIN exome AF: 0.384

Gnomad NFE exome AF: 0.410

Gnomad OTH exome AF: 0.396

GnomAD4 exome AF: 0.393 AC: 573864 AN: 1461856 Hom.: 114145 Cov.: 79 AF XY: 0.393 AC XY: 285692 AN XY: 727222

Gnomad4 AFR exome AF: 0.388

Gnomad4 AMR exome AF: 0.309

Gnomad4 ASJ exome AF: 0.408

Gnomad4 EAS exome AF: 0.182

Gnomad4 SAS exome AF: 0.388

Gnomad4 FIN exome AF: 0.386

Gnomad4 NFE exome AF: 0.404

Gnomad4 OTH exome AF: 0.388

GnomAD4 genome AF: 0.389 AC: 59176 AN: 152094 Hom.: 11732 Cov.: 33 AF XY: 0.386 AC XY: 28732 AN XY: 74342

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.403

Alfa AF: 0.405 Hom.: 9910

Bravo AF: 0.385

Asia WGS AF: 0.328 AC: 1140 AN: 3478

EpiCase AF: 0.418

EpiControl AF: 0.421

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Aural atresia, congenital Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 17, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.0090
Dann	Benign	0.31

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: rs3809997; hg19: chr18-72998886; COSMIC: COSV59007237; COSMIC: COSV59007237;