18-75211879-G-A

Variant names:

• chr18-75211879-G-A
• NM_001308210.2:c.3G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PVS1_Supporting PM2

The NM_001308210.2(TSHZ1):​c.3G>A​(p.Met1?) variant causes a start lost change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TSHZ1 NM_001308210.2 start_lost
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.24
• Publications: 0 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: Ambry Genetics, Illumina, G2P, Labcorp Genetics (formerly Invitae), ClinGen
• congenital vertical talus

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 46 codons. Genomic position: 75285543. Lost 0.042 part of the original CDS.
• PM2: Very rare variant in population databases, with high coverage

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.3G>A	p.Met1?	start_lost	Exon 1 of 2	NP_001295139.1	Q6ZSZ6-1
	TSHZ1	NM_005786.6		c.-96+636G>A		intron	N/A	NP_005777.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSHZ1	ENST00000580243.3	TSL:2 MANE Select	c.3G>A	p.Met1?	start_lost	Exon 1 of 2	ENSP00000464391.1	Q6ZSZ6-1
	TSHZ1	ENST00000322038.5	TSL:1	c.-96+636G>A		intron	N/A	ENSP00000323584.5	Q6ZSZ6-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1040860 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 491016

African (AFR) AF: 0.00 AC: 0 AN: 21412

American (AMR) AF: 0.00 AC: 0 AN: 7068

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12460

East Asian (EAS) AF: 0.00 AC: 0 AN: 22988

South Asian (SAS) AF: 0.00 AC: 0 AN: 19206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19800

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 894572

Other (OTH) AF: 0.00 AC: 0 AN: 40656

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Aural atresia, congenital (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.63	D
PhyloP100		5.2
Sift4G	Benign	0.27	T
Vest4		0.59
MVP		0.77
GERP RS		1.2
Varity_R		0.26
gMVP		0.28
Mutation Taster		=15/185	disease causing

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

hg19: chr18-72923834;