rs12460170

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-53166239-A-G
• chr19-53166239-A-T

Variant summary

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

The NM_024733.5(ZNF665):​c.251T>C​(p.Val84Ala) 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 1,613,672 control chromosomes in the GnomAD database, including 305,082 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 (22946 hom., cov: 32)
  • Exomes 𝑓: 0.62 (282136 hom.)
• Consequence: ZNF665 NM_024733.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• Publications: 31 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=2.1620522E-6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF665	NM_024733.5	c.251T>C	p.Val84Ala	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>C	p.Val84Ala	missense_variant	Exon 4 of 4	2	NM_024733.5	ENSP00000379702.2
ZNF665	ENST00000650736.1	c.251T>C	p.Val84Ala	missense_variant	Exon 5 of 5			ENSP00000498600.1
ZNF665	ENST00000600412.1	c.56T>C	p.Val19Ala	missense_variant	Exon 2 of 2	5		ENSP00000469154.1

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78436 AN: 151966 Hom.: 22934 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.518

GnomAD2 exomes AF: 0.624 AC: 155501 AN: 249198 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: 0.663

Gnomad FIN exome AF: 0.677

Gnomad NFE exome AF: 0.619

Gnomad OTH exome AF: 0.610

GnomAD4 exome AF: 0.616 AC: 900457 AN: 1461588 Hom.: 282136 Cov.: 59 AF XY: 0.620 AC XY: 450496 AN XY: 727062

African (AFR) AF: 0.207 AC: 6918 AN: 33476

American (AMR) AF: 0.718 AC: 32121 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 13077 AN: 26130

East Asian (EAS) AF: 0.685 AC: 27203 AN: 39694

South Asian (SAS) AF: 0.715 AC: 61664 AN: 86214

European-Finnish (FIN) AF: 0.674 AC: 36008 AN: 53388

Middle Eastern (MID) AF: 0.522 AC: 3010 AN: 5768

European-Non Finnish (NFE) AF: 0.616 AC: 684913 AN: 1111824

Other (OTH) AF: 0.589 AC: 35543 AN: 60372

GnomAD4 genome AF: 0.516 AC: 78477 AN: 152084 Hom.: 22946 Cov.: 32 AF XY: 0.524 AC XY: 38942 AN XY: 74324

African (AFR) AF: 0.229 AC: 9485 AN: 41506

American (AMR) AF: 0.616 AC: 9410 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1760 AN: 3470

East Asian (EAS) AF: 0.655 AC: 3392 AN: 5176

South Asian (SAS) AF: 0.715 AC: 3446 AN: 4818

European-Finnish (FIN) AF: 0.667 AC: 7035 AN: 10550

Middle Eastern (MID) AF: 0.459 AC: 134 AN: 292

European-Non Finnish (NFE) AF: 0.620 AC: 42143 AN: 67976

Other (OTH) AF: 0.520 AC: 1098 AN: 2112

Alfa AF: 0.574 Hom.: 78595

Bravo AF: 0.496

TwinsUK AF: 0.611 AC: 2266

ALSPAC AF: 0.603 AC: 2323

ESP6500AA AF: 0.224 AC: 870

ESP6500EA AF: 0.607 AC: 5044

ExAC AF: 0.617 AC: 74565

EpiCase AF: 0.606

EpiControl AF: 0.592

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.2
DANN	Benign	0.21
DEOGEN2	Benign	0.0025	.;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.00096	N
LIST_S2	Benign	0.0096	T;T
MetaRNN	Benign	0.0000022	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;N
PhyloP100		-0.027
PrimateAI	Benign	0.20	T
PROVEAN	Benign	1.5	N;.
REVEL	Benign	0.032
Sift	Benign	0.33	T;.
Sift4G	Benign	0.74	T;T
Polyphen		0.0	B;.
Vest4		0.023
MPC		0.032
ClinPred		0.0065	T
GERP RS		0.40
Varity_R		0.083
gMVP		0.023
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: rs12460170; hg19: chr19-53669492; COSMIC: COSV67215082; COSMIC: COSV67215082;