rs8074277

chr17-82831752-T-Cchr17-82831752-T-G

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.703A>G(p.Met235Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,613,822 control chromosomes in the GnomAD database, including 25,228 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.17 (2331 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22897 hom.)
• Consequence: ZNF750 NM_024702.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.11

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 (MetaRNN=0.0019102395).
• BP6: Variant 17-82831752-T-C is Benign according to our data. Variant chr17-82831752-T-C is described in ClinVar as [Benign]. Clinvar id is 3060121.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF750	NM_024702.3	c.703A>G	p.Met235Val	missense_variant	2/3	ENST00000269394.4
TBCD	NM_005993.5	c.1318+16818T>C		intron_variant		ENST00000355528.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF750	ENST00000269394.4	c.703A>G	p.Met235Val	missense_variant	2/3	1	NM_024702.3	P1
TBCD	ENST00000355528.9	c.1318+16818T>C		intron_variant		1	NM_005993.5	P1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25600 AN: 151834 Hom.: 2328 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0824

Gnomad SAS AF: 0.0474

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.151

GnomAD3 exomes AF: 0.175 AC: 43914 AN: 251358 Hom.: 4573 AF XY: 0.165 AC XY: 22479 AN XY: 135882

Gnomad AFR exome AF: 0.132

Gnomad AMR exome AF: 0.293

Gnomad ASJ exome AF: 0.137

Gnomad EAS exome AF: 0.0824

Gnomad SAS exome AF: 0.0578

Gnomad FIN exome AF: 0.243

Gnomad NFE exome AF: 0.182

Gnomad OTH exome AF: 0.168

GnomAD4 exome AF: 0.171 AC: 250160 AN: 1461870 Hom.: 22897 Cov.: 38 AF XY: 0.168 AC XY: 121883 AN XY: 727236

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.285

Gnomad4 ASJ exome AF: 0.138

Gnomad4 EAS exome AF: 0.0738

Gnomad4 SAS exome AF: 0.0584

Gnomad4 FIN exome AF: 0.235

Gnomad4 NFE exome AF: 0.178

Gnomad4 OTH exome AF: 0.163

GnomAD4 genome AF: 0.169 AC: 25620 AN: 151952 Hom.: 2331 Cov.: 32 AF XY: 0.169 AC XY: 12514 AN XY: 74262

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.0826

Gnomad4 SAS AF: 0.0473

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.149

Alfa AF: 0.166 Hom.: 5456

Bravo AF: 0.170

TwinsUK AF: 0.182 AC: 675

ALSPAC AF: 0.172 AC: 662

ESP6500AA AF: 0.131 AC: 577

ESP6500EA AF: 0.178 AC: 1534

ExAC AF: 0.169 AC: 20541

Asia WGS AF: 0.0610 AC: 215 AN: 3478

EpiCase AF: 0.166

EpiControl AF: 0.158

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

ZNF750-related condition Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.0020
Dann	Benign	0.53
DEOGEN2	Benign	0.00092	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.60	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.22	N
MutationTaster	Benign	0.98	P;P;P;P;P
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.23	N
REVEL	Benign	0.034
Sift	Benign	0.87	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.019
MPC		0.21
ClinPred		0.0077	T
GERP RS		-11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.058
gMVP		0.13

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: rs8074277; hg19: chr17-80789628; COSMIC: COSV53960502;