chr19-36877771-A-T

Position:

• chr19-36877771-A-T

Variant summary

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

The NM_001242472.2(ZNF345):​c.941A>T​(p.Tyr314Phe) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF345 NM_001242472.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0820

Genes affected

ZNF345 (HGNC:16367): (zinc finger protein 345) Enables sequence-specific double-stranded 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11955741).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF345	NM_001242472.2	c.941A>T	p.Tyr314Phe	missense_variant	3/3	ENST00000420450.6	NP_001229401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF345	ENST00000420450.6	c.941A>T	p.Tyr314Phe	missense_variant	3/3	1	NM_001242472.2	ENSP00000431216	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Aug 28, 2023

The c.941A>T (p.Y314F) alteration is located in exon 3 (coding exon 1) of the ZNF345 gene. This alteration results from a A to T substitution at nucleotide position 941, causing the tyrosine (Y) at amino acid position 314 to be replaced by a phenylalanine (F). 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	0.15
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.22	T;T;T;T;T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.050	.;.;.;.;T;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.12	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.25	N;N;N;N;N;.
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.5	.;.;N;N;.;.
REVEL	Benign	0.079
Sift	Benign	0.14	.;.;T;T;.;.
Sift4G	Benign	0.11	T;T;T;T;T;.
Polyphen		0.39	B;B;B;B;B;.
Vest4		0.20
MutPred		0.57		Gain of ubiquitination at K312 (P = 0.1028);Gain of ubiquitination at K312 (P = 0.1028);Gain of ubiquitination at K312 (P = 0.1028);Gain of ubiquitination at K312 (P = 0.1028);Gain of ubiquitination at K312 (P = 0.1028);.;
MVP		0.54
MPC		0.50
ClinPred		0.35	T
GERP RS		3.7
Varity_R		0.14
gMVP		0.032

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: chr19-37368673;