rs4801958

Positions:

• chr19-53164551-C-G
• chr19-53164551-C-T

Variant summary

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

The NM_024733.5(ZNF665):​c.1939G>C​(p.Val647Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V647I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF665 NM_024733.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

Genes affected

ZNF665 (HGNC:25885): (zinc finger protein 665) 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 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=0.12004772).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF665	NM_024733.5	c.1939G>C	p.Val647Leu	missense_variant	4/4	ENST00000396424.5	NP_079009.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF665	ENST00000396424.5	c.1939G>C	p.Val647Leu	missense_variant	4/4	2	NM_024733.5	ENSP00000379702.2
ZNF665	ENST00000650736.1	c.1939G>C	p.Val647Leu	missense_variant	5/5			ENSP00000498600.1
ZNF665	ENST00000600412.1	c.1744G>C	p.Val582Leu	missense_variant	2/2	5		ENSP00000469154.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 49

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.5
DANN	Benign	0.84
DEOGEN2	Benign	0.010	.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.00059	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	.;L
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.77	N;.
REVEL	Benign	0.017
Sift	Benign	0.16	T;.
Sift4G	Uncertain	0.044	D;D
Polyphen		0.0020	B;.
Vest4		0.040
MutPred		0.57		Loss of methylation at K652 (P = 0.0778);.;
MVP		0.11
MPC		0.030
ClinPred		0.050	T
GERP RS		2.7
Varity_R		0.10
gMVP		0.036

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

LitVar

Other links and lift over

dbSNP: rs4801958; hg19: chr19-53667804;