rs12450046

Positions:

• chr17-82832512-G-A
• chr17-82832512-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_024702.3(ZNF750):​c.-58C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,487,512 control chromosomes in the GnomAD database, including 22,965 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2308 hom., cov: 32)
  • Exomes 𝑓: 0.17 (20657 hom.)
• Consequence: ZNF750 NM_024702.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.497

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 17-82832512-G-A is Benign according to our data. Variant chr17-82832512-G-A is described in ClinVar as [Benign]. Clinvar id is 1227535.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF750	NM_024702.3	c.-58C>T		5_prime_UTR_variant	2/3	ENST00000269394.4
TBCD	NM_005993.5	c.1318+17578G>A		intron_variant		ENST00000355528.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF750	ENST00000269394.4	c.-58C>T		5_prime_UTR_variant	2/3	1	NM_024702.3	P1
TBCD	ENST00000355528.9	c.1318+17578G>A		intron_variant		1	NM_005993.5	P1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25405 AN: 151974 Hom.: 2305 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0822

Gnomad SAS AF: 0.0428

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.150

GnomAD4 exome AF: 0.169 AC: 226190 AN: 1335420 Hom.: 20657 Cov.: 21 AF XY: 0.165 AC XY: 110900 AN XY: 670752

Gnomad4 AFR exome AF: 0.129

Gnomad4 AMR exome AF: 0.284

Gnomad4 ASJ exome AF: 0.137

Gnomad4 EAS exome AF: 0.0736

Gnomad4 SAS exome AF: 0.0511

Gnomad4 FIN exome AF: 0.229

Gnomad4 NFE exome AF: 0.178

Gnomad4 OTH exome AF: 0.162

GnomAD4 genome AF: 0.167 AC: 25426 AN: 152092 Hom.: 2308 Cov.: 32 AF XY: 0.167 AC XY: 12411 AN XY: 74358

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.0824

Gnomad4 SAS AF: 0.0427

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.148

Alfa AF: 0.172 Hom.: 2362

Bravo AF: 0.168

Asia WGS AF: 0.0600 AC: 210 AN: 3478

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

May 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.7
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs12450046; hg19: chr17-80790388; COSMIC: COSV53960652;