19-53164551-C-T

Variant names:

• chr19-53164551-C-T
• rs4801958
• NM_024733.5:c.1939G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001353458.2(ZNF665):​c.2023G>A​(p.Val675Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 1,613,352 control chromosomes in the GnomAD database, including 305,094 homozygotes. 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.

• Frequency:
  • Genomes: 𝑓 0.52 (22966 hom., cov: 33)
  • Exomes 𝑓: 0.62 (282128 hom.)
• Consequence: ZNF665 NM_001353458.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 26 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.0616925E-6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353458.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF665	NM_024733.5	MANE Select	c.1939G>A	p.Val647Ile	missense	Exon 4 of 4	NP_079009.3
	ZNF665	NM_001353458.2		c.2023G>A	p.Val675Ile	missense	Exon 5 of 5	NP_001340387.1
	ZNF665	NM_001353459.2		c.1939G>A	p.Val647Ile	missense	Exon 4 of 4	NP_001340388.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF665	ENST00000396424.5	TSL:2 MANE Select	c.1939G>A	p.Val647Ile	missense	Exon 4 of 4	ENSP00000379702.2
	ZNF665	ENST00000650736.1		c.1939G>A	p.Val647Ile	missense	Exon 5 of 5	ENSP00000498600.1
	ZNF665	ENST00000868912.1		c.1939G>A	p.Val647Ile	missense	Exon 4 of 4	ENSP00000538971.1

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78466 AN: 151860 Hom.: 22955 Cov.: 33

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.520

GnomAD2 exomes AF: 0.623 AC: 156233 AN: 250650 AF XY: 0.629

Gnomad AFR exome AF: 0.215

Gnomad AMR exome AF: 0.731

Gnomad ASJ exome AF: 0.496

Gnomad EAS exome AF: 0.661

Gnomad FIN exome AF: 0.677

Gnomad NFE exome AF: 0.619

Gnomad OTH exome AF: 0.609

GnomAD4 exome AF: 0.616 AC: 900308 AN: 1461374 Hom.: 282128 Cov.: 49 AF XY: 0.620 AC XY: 450437 AN XY: 726984

African (AFR) AF: 0.207 AC: 6916 AN: 33476

American (AMR) AF: 0.718 AC: 32110 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 13082 AN: 26124

East Asian (EAS) AF: 0.685 AC: 27185 AN: 39696

South Asian (SAS) AF: 0.715 AC: 61661 AN: 86208

European-Finnish (FIN) AF: 0.674 AC: 36018 AN: 53408

Middle Eastern (MID) AF: 0.522 AC: 3008 AN: 5766

European-Non Finnish (NFE) AF: 0.616 AC: 684793 AN: 1111616

Other (OTH) AF: 0.589 AC: 35535 AN: 60374

GnomAD4 genome AF: 0.517 AC: 78504 AN: 151978 Hom.: 22966 Cov.: 33 AF XY: 0.525 AC XY: 38956 AN XY: 74248

African (AFR) AF: 0.229 AC: 9480 AN: 41422

American (AMR) AF: 0.616 AC: 9411 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1760 AN: 3466

East Asian (EAS) AF: 0.656 AC: 3384 AN: 5160

South Asian (SAS) AF: 0.715 AC: 3449 AN: 4826

European-Finnish (FIN) AF: 0.668 AC: 7057 AN: 10564

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.620 AC: 42159 AN: 67956

Other (OTH) AF: 0.521 AC: 1096 AN: 2104

Alfa AF: 0.578 Hom.: 69926

Bravo AF: 0.496

TwinsUK AF: 0.612 AC: 2269

ALSPAC AF: 0.603 AC: 2324

ESP6500AA AF: 0.232 AC: 1021

ESP6500EA AF: 0.610 AC: 5242

ExAC AF: 0.615 AC: 74673

Asia WGS AF: 0.645 AC: 2243 AN: 3478

EpiCase AF: 0.606

EpiControl AF: 0.592

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.88	T
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.17
DANN	Benign	0.076
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.00054	N
LIST_S2	Benign	0.34	T
MetaRNN	Benign	0.0000031	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.49	N
PhyloP100		-1.3
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.38	N
REVEL	Benign	0.029
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.045
MPC		0.026
ClinPred		0.0010	T
GERP RS		2.7
Varity_R		0.069
gMVP		0.021
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4801958; hg19: chr19-53667804; COSMIC: COSV67215054; COSMIC: COSV67215054;