19-53166239-A-T

Variant names:

• chr19-53166239-A-T
• rs12460170
• NM_024733.5:c.251T>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024733.5(ZNF665):​c.251T>A​(p.Val84Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,660 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V84A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF665 NM_024733.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270

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 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=0.04162404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF665	NM_024733.5	c.251T>A	p.Val84Glu	missense_variant	Exon 4 of 4	ENST00000396424.5	NP_079009.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF665	ENST00000396424.5	c.251T>A	p.Val84Glu	missense_variant	Exon 4 of 4	2	NM_024733.5	ENSP00000379702.2
ZNF665	ENST00000650736.1	c.251T>A	p.Val84Glu	missense_variant	Exon 5 of 5			ENSP00000498600.1
ZNF665	ENST00000600412.1	c.56T>A	p.Val19Glu	missense_variant	Exon 2 of 2	5		ENSP00000469154.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461660 Hom.: 0 Cov.: 59 AF XY: 0.00000138 AC XY: 1 AN XY: 727102

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.3
DANN	Benign	0.16
DEOGEN2	Benign	0.0012	.;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.000090	N
LIST_S2	Benign	0.011	T;T
M_CAP	Benign	0.00039	T
MetaRNN	Benign	0.042	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.6	.;N
PrimateAI	Benign	0.20	T
PROVEAN	Benign	3.6	N;.
REVEL	Benign	0.036
Sift	Benign	1.0	T;.
Sift4G	Benign	0.60	T;T
Polyphen		0.0	B;.
Vest4		0.055
MutPred		0.59		Gain of disorder (P = 0.0061);.;
MVP		0.14
MPC		0.038
ClinPred		0.070	T
GERP RS		0.40
Varity_R		0.14
gMVP		0.043

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: rs12460170; hg19: chr19-53669492; COSMIC: COSV67216446; COSMIC: COSV67216446;