chr17-82829995-TTTTG-T

Position:

• chr17-82829995-TTTTG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_024702.3(ZNF750):​c.*143_*146del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 1,235,914 control chromosomes in the GnomAD database, including 140,998 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.40 (13573 hom., cov: 0)
  • Exomes 𝑓: 0.47 (127425 hom.)
• Consequence: ZNF750 NM_024702.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.427

Genes affected

ZNF750 (HGNC:25843): (zinc finger protein 750) This gene encodes a protein with a nuclear localization site and a C2H2 zinc finger domain. Mutations in this gene have been associated with seborrhea-like dermatitis with psoriasiform elements. [provided by RefSeq, Jul 2008]

TBCD (HGNC:11581): (tubulin folding cofactor D) Cofactor D is one of four proteins (cofactors A, D, E, and C) involved in the pathway leading to correctly folded beta-tubulin from folding intermediates. Cofactors A and D are believed to play a role in capturing and stabilizing beta-tubulin intermediates in a quasi-native confirmation. Cofactor E binds to the cofactor D/beta-tubulin complex; interaction with cofactor C then causes the release of beta-tubulin polypeptides that are committed to the native state. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 17-82829995-TTTTG-T is Benign according to our data. Variant chr17-82829995-TTTTG-T is described in ClinVar as [Benign]. Clinvar id is 1249122.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF750	NM_024702.3	c.*143_*146del		3_prime_UTR_variant	3/3	ENST00000269394.4
TBCD	NM_005993.5	c.1318+15081_1318+15084del		intron_variant		ENST00000355528.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF750	ENST00000269394.4	c.*143_*146del		3_prime_UTR_variant	3/3	1	NM_024702.3	P1
TBCD	ENST00000355528.9	c.1318+15081_1318+15084del		intron_variant		1	NM_005993.5	P1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 60869 AN: 151564 Hom.: 13575 Cov.: 0

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.446

GnomAD4 exome AF: 0.474 AC: 513447 AN: 1084230 Hom.: 127425 AF XY: 0.481 AC XY: 259052 AN XY: 538726

Gnomad4 AFR exome AF: 0.192

Gnomad4 AMR exome AF: 0.313

Gnomad4 ASJ exome AF: 0.557

Gnomad4 EAS exome AF: 0.517

Gnomad4 SAS exome AF: 0.621

Gnomad4 FIN exome AF: 0.447

Gnomad4 NFE exome AF: 0.473

Gnomad4 OTH exome AF: 0.472

GnomAD4 genome AF: 0.401 AC: 60876 AN: 151684 Hom.: 13573 Cov.: 0 AF XY: 0.405 AC XY: 30011 AN XY: 74088

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.628

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.444

Bravo AF: 0.385

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs142352768; hg19: chr17-80787871;