chr10-38054641-T-G

Position:

• chr10-38054641-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006954.2(ZNF33A):​c.517T>G​(p.Cys173Gly) 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 pathogenic 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)
• Consequence: ZNF33A NM_006954.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.99

Genes affected

ZNF33A (HGNC:13096): (zinc finger protein 33A) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.793

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF33A	NM_006954.2	c.517T>G	p.Cys173Gly	missense_variant	5/5	ENST00000432900.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF33A	ENST00000432900.7	c.517T>G	p.Cys173Gly	missense_variant	5/5	1	NM_006954.2	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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 17, 2024

The c.517T>G (p.C173G) alteration is located in exon 5 (coding exon 4) of the ZNF33A gene. This alteration results from a T to G substitution at nucleotide position 517, causing the cysteine (C) at amino acid position 173 to be replaced by a glycine (G). 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	0.078
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.099	T;.;.;.;T
Eigen	Benign	-0.087
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.46	T;T;T;T;T
M_CAP	Benign	0.0039	T
MetaRNN	Pathogenic	0.79	D;D;D;D;D
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.7	.;.;.;.;M
MutationTaster	Benign	0.68	N;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-5.1	.;.;.;.;D
REVEL	Benign	0.18
Sift	Benign	0.19	.;.;.;.;T
Sift4G	Uncertain	0.015	D;D;D;D;D
Polyphen		0.80	.;.;.;.;P
Vest4		0.23
MutPred		0.81		.;.;.;.;Loss of stability (P = 0.0055);
MVP		0.77
MPC		0.15
ClinPred		0.97	D
GERP RS		2.3
Varity_R		0.14
gMVP		0.065

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: chr10-38343569;