17-82832566-T-G

Position:

• chr17-82832566-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024702.3(ZNF750):​c.-112A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 943,716 control chromosomes in the GnomAD database, including 321,698 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.81 (49787 hom., cov: 33)
  • Exomes 𝑓: 0.83 (271911 hom.)
• Consequence: ZNF750 NM_024702.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.919

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 17-82832566-T-G is Benign according to our data. Variant chr17-82832566-T-G is described in ClinVar as [Benign]. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF750	NM_024702.3	c.-112A>C		5_prime_UTR_variant	2/3	ENST00000269394.4	NP_078978.2
TBCD	NM_005993.5	c.1318+17632T>G		intron_variant		ENST00000355528.9	NP_005984.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF750	ENST00000269394.4	c.-112A>C		5_prime_UTR_variant	2/3	1	NM_024702.3	ENSP00000269394	P1
TBCD	ENST00000355528.9	c.1318+17632T>G		intron_variant		1	NM_005993.5	ENSP00000347719	P1

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122565 AN: 152086 Hom.: 49752 Cov.: 33

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.769

Gnomad EAS AF: 0.920

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.820

GnomAD4 exome AF: 0.826 AC: 654087 AN: 791512 Hom.: 271911 Cov.: 11 AF XY: 0.820 AC XY: 339552 AN XY: 414070

Gnomad4 AFR exome AF: 0.718

Gnomad4 AMR exome AF: 0.917

Gnomad4 ASJ exome AF: 0.767

Gnomad4 EAS exome AF: 0.902

Gnomad4 SAS exome AF: 0.685

Gnomad4 FIN exome AF: 0.844

Gnomad4 NFE exome AF: 0.840

Gnomad4 OTH exome AF: 0.819

GnomAD4 genome AF: 0.806 AC: 122659 AN: 152204 Hom.: 49787 Cov.: 33 AF XY: 0.806 AC XY: 60012 AN XY: 74426

Gnomad4 AFR AF: 0.719

Gnomad4 AMR AF: 0.885

Gnomad4 ASJ AF: 0.769

Gnomad4 EAS AF: 0.919

Gnomad4 SAS AF: 0.687

Gnomad4 FIN AF: 0.848

Gnomad4 NFE AF: 0.835

Gnomad4 OTH AF: 0.822

Alfa AF: 0.831 Hom.: 69876

Bravo AF: 0.808

Asia WGS AF: 0.792 AC: 2758 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.3
DANN	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs3744165; hg19: chr17-80790442;