chr17-82830205-C-G

Position:

• chr17-82830205-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024702.3(ZNF750):​c.2109G>C​(p.Lys703Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF750 NM_024702.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0170

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35875595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF750	NM_024702.3	c.2109G>C	p.Lys703Asn	missense_variant	3/3	ENST00000269394.4	NP_078978.2
TBCD	NM_005993.5	c.1318+15271C>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.2109G>C	p.Lys703Asn	missense_variant	3/3	1	NM_024702.3	ENSP00000269394	P1
TBCD	ENST00000355528.9	c.1318+15271C>G		intron_variant		1	NM_005993.5	ENSP00000347719	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Oct 26, 2022

The c.2109G>C (p.K703N) alteration is located in exon 3 (coding exon 2) of the ZNF750 gene. This alteration results from a G to C substitution at nucleotide position 2109, causing the lysine (K) at amino acid position 703 to be replaced by an asparagine (N). 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	Pathogenic	0.85
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;T
Eigen	Benign	0.16
Eigen_PC	Benign	0.061
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.7	M;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.3	N;.
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0	D;T
Polyphen		1.0	D;.
Vest4		0.48
MutPred		0.25		Gain of ubiquitination at K704 (P = 0.0163);.;
MVP		0.23
MPC		0.78
ClinPred		0.99	D
GERP RS		2.9
Varity_R		0.34
gMVP		0.28

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: chr17-80788081; COSMIC: COSV53959762;