19-55613973-G-C

Position:

• chr19-55613973-G-C

Variant summary

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

The NM_001195605.2(ZNF865):​c.355G>C​(p.Ala119Pro) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZNF865 NM_001195605.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.881

Genes affected

ZNF865 (HGNC:38705): (zinc finger protein 865) Predicted to enable DNA-binding transcription factor activity 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 located 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=0.10539514).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF865	NM_001195605.2	c.355G>C	p.Ala119Pro	missense_variant	2/2	ENST00000568956.2	NP_001182534.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF865	ENST00000568956.2	c.355G>C	p.Ala119Pro	missense_variant	2/2	2	NM_001195605.2	ENSP00000457715	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

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

Apr 27, 2022

The c.355G>C (p.A119P) alteration is located in exon 1 (coding exon 1) of the ZNF865 gene. This alteration results from a G to C substitution at nucleotide position 355, causing the alanine (A) at amino acid position 119 to be replaced by a proline (P). 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	0.081
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0039	T
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.24	T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.11	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.47	N
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.010	D
Vest4		0.22
MVP		0.47
GERP RS		1.9
Varity_R		0.12
gMVP		0.16

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: chr19-56125339;