chr17-82830608-G-C

Position:

• chr17-82830608-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024702.3(ZNF750):​c.1706C>G​(p.Pro569Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF750 NM_024702.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.493

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07098773).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF750	NM_024702.3	c.1706C>G	p.Pro569Arg	missense_variant	3/3	ENST00000269394.4
TBCD	NM_005993.5	c.1318+15674G>C		intron_variant		ENST00000355528.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF750	ENST00000269394.4	c.1706C>G	p.Pro569Arg	missense_variant	3/3	1	NM_024702.3	P1
TBCD	ENST00000355528.9	c.1318+15674G>C		intron_variant		1	NM_005993.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461748 Hom.: 0 Cov.: 120 AF XY: 0.00000138 AC XY: 1 AN XY: 727186

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 16, 2023

The c.1706C>G (p.P569R) alteration is located in exon 3 (coding exon 2) of the ZNF750 gene. This alteration results from a C to G substitution at nucleotide position 1706, causing the proline (P) at amino acid position 569 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.0
DANN	Benign	0.54
DEOGEN2	Benign	0.0045	T;T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.32	T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.071	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.7	D;.
REVEL	Benign	0.053
Sift	Benign	0.12	T;.
Sift4G	Benign	0.41	T;T
Polyphen		0.0010	B;.
Vest4		0.036
MutPred		0.24		Gain of MoRF binding (P = 0.004);.;
MVP		0.043
MPC		0.22
ClinPred		0.053	T
GERP RS		0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.4
Varity_R		0.034
gMVP		0.066

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-80788484;