chr20-33788887-T-C

Position:

• chr20-33788887-T-C

Variant summary

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

The ENST00000375200.6(ZNF341):​c.1877T>C​(p.Val626Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF341 ENST00000375200.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.49

Genes affected

ZNF341 (HGNC:15992): (zinc finger protein 341) Enables DNA binding activity and DNA-binding transcription activator activity. Predicted to be involved in regulation of transcription, DNA-templated. Located in nucleus. Implicated in hyper IgE recurrent infection syndrome 3. [provided by Alliance of Genome Resources, Apr 2022]

ZNF341 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF341	NM_001282933.2	c.1877T>C	p.Val626Ala	missense_variant	13/15	ENST00000375200.6	NP_001269862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF341	ENST00000375200.6	c.1877T>C	p.Val626Ala	missense_variant	13/15	1	NM_001282933.2	ENSP00000364346.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 12, 2023

This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 619 of the ZNF341 protein (p.Val619Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ZNF341-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.029	.;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.81	T;D
M_CAP	Benign	0.0098	T
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	.;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.93	N;N
REVEL	Benign	0.17
Sift	Benign	0.76	T;T
Sift4G	Benign	0.58	T;T
Polyphen		0.94	P;P
Vest4		0.54
MutPred		0.48		.;Gain of disorder (P = 0.0265);
MVP		0.46
MPC		0.48
ClinPred		0.95	D
GERP RS		4.7
Varity_R		0.077
gMVP		0.40

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: chr20-32376693;