rs543956737

Variant names:

• chr18-75285607-C-G
• 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. Variant got -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06741786).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSHZ1	NM_001308210.2	c.200C>G	p.Ala67Gly	missense_variant	Exon 2 of 2	ENST00000580243.3	NP_001295139.1
TSHZ1	NM_005786.6	c.65C>G	p.Ala22Gly	missense_variant	Exon 2 of 2		NP_005777.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSHZ1	ENST00000580243.3	c.200C>G	p.Ala67Gly	missense_variant	Exon 2 of 2	2	NM_001308210.2	ENSP00000464391.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.067	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.0	.;L;.;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.17	N;.;N;N
REVEL	Benign	0.14
Sift	Benign	0.089	T;.;T;T
Sift4G	Benign	0.37	T;T;T;D
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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-72997562;