rs543956737

Variant names:

• chr18-75285607-C-G
• rs543956737
• NM_001308210.2:c.200C>G

Your query was ambiguous. Multiple possible variants found:

• chr18-75285607-C-G
• chr18-75285607-C-T

Variant summary

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

The NM_001308210.2(TSHZ1):​c.200C>G​(p.Ala67Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A67V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TSHZ1 NM_001308210.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.97
• 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: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Illumina
• congenital vertical talus

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

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 (MetaRNN=0.06741786).

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.200C>G	p.Ala67Gly	missense	Exon 2 of 2	NP_001295139.1
	TSHZ1	NM_005786.6		c.65C>G	p.Ala22Gly	missense	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.200C>G	p.Ala67Gly	missense	Exon 2 of 2	ENSP00000464391.1
	TSHZ1	ENST00000322038.5	TSL:1	c.65C>G	p.Ala22Gly	missense	Exon 2 of 2	ENSP00000323584.5
	TSHZ1	ENST00000560918.2	TSL:4	c.65C>G	p.Ala22Gly	missense	Exon 2 of 2	ENSP00000453834.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459400 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725500

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39622

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110356

Other (OTH) AF: 0.00 AC: 0 AN: 60274

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	17
DANN	Benign	0.88
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.72
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.0	L
PhyloP100		5.0
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.14
Sift	Benign	0.089	T
Sift4G	Benign	0.37	T
Polyphen		0.0030	B
Vest4		0.17
MutPred		0.059		Gain of glycosylation at S66 (P = 0.0972)
MVP		0.20
MPC		0.34
ClinPred		0.24	T
GERP RS		3.5
Varity_R		0.037
gMVP		0.20
Mutation Taster		=91/9	polymorphism

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: rs543956737; hg19: chr18-72997562;