NM_001308210.2:c.40+4864T>G

Variant names:

• chr18-75216780-T-G
• rs2639974
• NM_001308210.2:c.40+4864T>G

Variant summary

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

The NM_001308210.2(TSHZ1):​c.40+4864T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 152,006 control chromosomes in the GnomAD database, including 12,665 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 0.39 (12665 hom., cov: 33)
• Consequence: TSHZ1 NM_001308210.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.544 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSHZ1	NM_001308210.2	MANE Select	c.40+4864T>G		intron	N/A	NP_001295139.1
	TSHZ1	NM_005786.6		c.-96+5537T>G		intron	N/A	NP_005777.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSHZ1	ENST00000580243.3	TSL:2 MANE Select	c.40+4864T>G		intron	N/A	ENSP00000464391.1
	TSHZ1	ENST00000322038.5	TSL:1	c.-96+5537T>G		intron	N/A	ENSP00000323584.5

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59940 AN: 151888 Hom.: 12638 Cov.: 33

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.395 AC: 60024 AN: 152006 Hom.: 12665 Cov.: 33 AF XY: 0.397 AC XY: 29503 AN XY: 74300

African (AFR) AF: 0.550 AC: 22818 AN: 41456

American (AMR) AF: 0.359 AC: 5482 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 917 AN: 3462

East Asian (EAS) AF: 0.423 AC: 2174 AN: 5140

South Asian (SAS) AF: 0.322 AC: 1550 AN: 4808

European-Finnish (FIN) AF: 0.371 AC: 3915 AN: 10562

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 22007 AN: 67980

Other (OTH) AF: 0.364 AC: 770 AN: 2114

Alfa AF: 0.356 Hom.: 19301

Bravo AF: 0.402

Asia WGS AF: 0.427 AC: 1482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.066
DANN	Benign	0.47
PhyloP100		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2639974; hg19: chr18-72928735;