chr19-58454312-T-C

Position:

• chr19-58454312-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_207395.3(ZNF324B):​c.206T>C​(p.Leu69Pro) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF324B NM_207395.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.45

Genes affected

ZNF324B (HGNC:33107): (zinc finger protein 324B) 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. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07369506).
• BP6: Variant 19-58454312-T-C is Benign according to our data. Variant chr19-58454312-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2264470.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF324B	NM_207395.3	c.206T>C	p.Leu69Pro	missense_variant	3/4	ENST00000336614.9	NP_997278.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF324B	ENST00000336614.9	c.206T>C	p.Leu69Pro	missense_variant	3/4	1	NM_207395.3	ENSP00000337473	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.33
DANN	Benign	0.69
DEOGEN2	Benign	0.026	T;T;.;.;.;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0032	N
LIST_S2	Benign	0.42	.;T;T;T;T;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.074	T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.76	N;N;.;.;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.070	N;N;.;.;.;.
REVEL	Benign	0.0080
Sift	Benign	0.34	T;T;.;.;.;.
Sift4G	Benign	0.39	T;T;T;T;T;T
Polyphen		0.0010	B;B;.;.;.;.
Vest4		0.077
MutPred		0.47		Gain of disorder (P = 0.0101);Gain of disorder (P = 0.0101);Gain of disorder (P = 0.0101);Gain of disorder (P = 0.0101);Gain of disorder (P = 0.0101);Gain of disorder (P = 0.0101);
MVP		0.067
MPC		1.2
ClinPred		0.26	T
GERP RS		-5.5
Varity_R		0.034
gMVP		0.076

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: chr19-58965679;