NM_001308210.2:c.315C>T

Variant names:

• chr18-75285722-C-T
• rs3826609
• NM_001308210.2:c.315C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001308210.2(TSHZ1):​c.315C>T​(p.Ser105Ser) 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:3
• Conservation: PhyloP100: 0.370
• Publications: 19 publications found

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]

TSHZ1 Gene-Disease associations (from GenCC):

• aural atresia, congenital

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Illumina
• congenital vertical talus

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 1260276.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308210.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSHZ1	NM_001308210.2	MANE Select	c.315C>T	p.Ser105Ser	synonymous	Exon 2 of 2	NP_001295139.1
	TSHZ1	NM_005786.6		c.180C>T	p.Ser60Ser	synonymous	Exon 2 of 2	NP_005777.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSHZ1	ENST00000580243.3	TSL:2 MANE Select	c.315C>T	p.Ser105Ser	synonymous	Exon 2 of 2	ENSP00000464391.1
	TSHZ1	ENST00000322038.5	TSL:1	c.180C>T	p.Ser60Ser	synonymous	Exon 2 of 2	ENSP00000323584.5
	TSHZ1	ENST00000560918.2	TSL:4	c.180C>T	p.Ser60Ser	synonymous	Exon 2 of 2	ENSP00000453834.2

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

GnomAD2 exomes AF: 0.263 AC: 65894 AN: 250932 AF XY: 0.266

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 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

African (AFR) AF: 0.0642 AC: 2148 AN: 33480

American (AMR) AF: 0.253 AC: 11311 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 7806 AN: 26126

East Asian (EAS) AF: 0.165 AC: 6562 AN: 39698

South Asian (SAS) AF: 0.210 AC: 18114 AN: 86242

European-Finnish (FIN) AF: 0.299 AC: 15942 AN: 53390

Middle Eastern (MID) AF: 0.275 AC: 1583 AN: 5766

European-Non Finnish (NFE) AF: 0.313 AC: 347566 AN: 1111818

Other (OTH) AF: 0.274 AC: 16538 AN: 60376

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

African (AFR) AF: 0.0734 AC: 3049 AN: 41514

American (AMR) AF: 0.299 AC: 4570 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1048 AN: 3472

East Asian (EAS) AF: 0.149 AC: 770 AN: 5162

South Asian (SAS) AF: 0.196 AC: 944 AN: 4814

European-Finnish (FIN) AF: 0.286 AC: 3018 AN: 10562

Middle Eastern (MID) AF: 0.236 AC: 69 AN: 292

European-Non Finnish (NFE) AF: 0.318 AC: 21607 AN: 67940

Other (OTH) AF: 0.248 AC: 524 AN: 2110

Alfa AF: 0.292 Hom.: 25389

Bravo AF: 0.228

Asia WGS AF: 0.195 AC: 679 AN: 3478

EpiCase AF: 0.325

EpiControl AF: 0.327

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	TSHZ1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.5
DANN	Benign	0.63
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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