NM_001308210.2:c.41-9914T>C

Variant names:

• chr18-75275534-T-C
• rs2581644
• NM_001308210.2:c.41-9914T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001308210.2(TSHZ1):​c.41-9914T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 152,154 control chromosomes in the GnomAD database, including 47,769 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.79 (47769 hom., cov: 32)
• Consequence: TSHZ1 NM_001308210.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSHZ1	NM_001308210.2	c.41-9914T>C		intron_variant	Intron 1 of 1	ENST00000580243.3	NP_001295139.1
TSHZ1	NM_005786.6	c.-95-9914T>C		intron_variant	Intron 1 of 1		NP_005777.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSHZ1	ENST00000580243.3	c.41-9914T>C		intron_variant	Intron 1 of 1	2	NM_001308210.2	ENSP00000464391.1
TSHZ1	ENST00000322038.5	c.-95-9914T>C		intron_variant	Intron 1 of 1	1		ENSP00000323584.5
TSHZ1	ENST00000560918.2	c.-95-9914T>C		intron_variant	Intron 1 of 1	4		ENSP00000453834.2
TSHZ1	ENST00000560661.1	c.-95-9914T>C		intron_variant	Intron 2 of 2	4		ENSP00000452718.1

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120208 AN: 152036 Hom.: 47716 Cov.: 32

Gnomad AFR AF: 0.813

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.876

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.775

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.791 AC: 120319 AN: 152154 Hom.: 47769 Cov.: 32 AF XY: 0.793 AC XY: 58944 AN XY: 74350

African (AFR) AF: 0.814 AC: 33767 AN: 41502

American (AMR) AF: 0.742 AC: 11340 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 2600 AN: 3466

East Asian (EAS) AF: 0.853 AC: 4417 AN: 5180

South Asian (SAS) AF: 0.877 AC: 4231 AN: 4824

European-Finnish (FIN) AF: 0.817 AC: 8640 AN: 10576

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.776 AC: 52776 AN: 68008

Other (OTH) AF: 0.770 AC: 1626 AN: 2112

Alfa AF: 0.777 Hom.: 75616

Bravo AF: 0.786

Asia WGS AF: 0.833 AC: 2897 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.59
DANN	Benign	0.29
PhyloP100		-2.1
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: rs2581644; hg19: chr18-72987489;