chr8-144773597-T-C

Position:

• chr8-144773597-T-C

Variant summary

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

The NM_001286769.2(ZNF34):​c.1289A>G​(p.Asp430Gly) 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. 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: ZNF34 NM_001286769.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.46

Genes affected

ZNF34 (HGNC:13098): (zinc finger protein 34) Predicted to enable DNA-binding transcription factor 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. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF34 (HGNC:):

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=0.18023416).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF34	NM_001286769.2	c.1289A>G	p.Asp430Gly	missense_variant	6/6	ENST00000429371.7	NP_001273698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF34	ENST00000429371.7	c.1289A>G	p.Asp430Gly	missense_variant	6/6	1	NM_001286769.2	ENSP00000396894.2
ZNF34	ENST00000343459.8	c.1352A>G	p.Asp451Gly	missense_variant	6/6	1		ENSP00000341528.5
ZNF34	ENST00000527740.1	n.1579A>G		non_coding_transcript_exon_variant	4/4	5

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

Jul 25, 2023

The c.1352A>G (p.D451G) alteration is located in exon 6 (coding exon 5) of the ZNF34 gene. This alteration results from a A to G substitution at nucleotide position 1352, causing the aspartic acid (D) at amino acid position 451 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	0.30
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.25	T;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.55	N;.
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-4.1	D;D
REVEL	Benign	0.097
Sift	Uncertain	0.016	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		0.13	B;.
Vest4		0.22
MutPred		0.58		Gain of catalytic residue at D451 (P = 0.0781);.;
MVP		0.35
MPC		0.72
ClinPred		0.77	D
GERP RS		3.5
Varity_R		0.35
gMVP		0.088

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: chr8-145998982;