NM_032689.5:c.1592A>G

Variant names:

• chr19-37698539-T-C
• rs958305
• NM_032689.5:c.1592A>G

Variant summary

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

The NM_032689.5(ZNF607):​c.1592A>G​(p.Lys531Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 1,613,740 control chromosomes in the GnomAD database, including 499,672 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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 0.71 (39491 hom., cov: 31)
  • Exomes 𝑓: 0.79 (460181 hom.)
• Consequence: ZNF607 NM_032689.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140
• Publications: 39 publications found

Genes affected

ZNF607 (HGNC:28192): (zinc finger protein 607) 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]

ENSG00000267552 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=7.8106626E-7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF607	NM_032689.5	c.1592A>G	p.Lys531Arg	missense_variant	Exon 5 of 5	ENST00000355202.9	NP_116078.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF607	ENST00000355202.9	c.1592A>G	p.Lys531Arg	missense_variant	Exon 5 of 5	2	NM_032689.5	ENSP00000347338.2
ENSG00000267552	ENST00000586606.6	n.346+1246A>G		intron_variant	Intron 5 of 6	3		ENSP00000467889.1

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107520 AN: 151794 Hom.: 39453 Cov.: 31

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.778

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.822

Gnomad OTH AF: 0.716

GnomAD2 exomes AF: 0.714 AC: 179413 AN: 251388 AF XY: 0.724

Gnomad AFR exome AF: 0.557

Gnomad AMR exome AF: 0.619

Gnomad ASJ exome AF: 0.785

Gnomad EAS exome AF: 0.303

Gnomad FIN exome AF: 0.784

Gnomad NFE exome AF: 0.816

Gnomad OTH exome AF: 0.769

GnomAD4 exome AF: 0.786 AC: 1149145 AN: 1461826 Hom.: 460181 Cov.: 75 AF XY: 0.785 AC XY: 571077 AN XY: 727212

African (AFR) AF: 0.549 AC: 18388 AN: 33480

American (AMR) AF: 0.628 AC: 28069 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 20471 AN: 26136

East Asian (EAS) AF: 0.296 AC: 11735 AN: 39698

South Asian (SAS) AF: 0.687 AC: 59276 AN: 86252

European-Finnish (FIN) AF: 0.786 AC: 41984 AN: 53400

Middle Eastern (MID) AF: 0.780 AC: 4501 AN: 5768

European-Non Finnish (NFE) AF: 0.826 AC: 918124 AN: 1111972

Other (OTH) AF: 0.772 AC: 46597 AN: 60396

GnomAD4 genome AF: 0.708 AC: 107607 AN: 151914 Hom.: 39491 Cov.: 31 AF XY: 0.704 AC XY: 52256 AN XY: 74248

African (AFR) AF: 0.564 AC: 23338 AN: 41400

American (AMR) AF: 0.676 AC: 10303 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2645 AN: 3472

East Asian (EAS) AF: 0.310 AC: 1599 AN: 5150

South Asian (SAS) AF: 0.654 AC: 3148 AN: 4812

European-Finnish (FIN) AF: 0.779 AC: 8225 AN: 10554

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.822 AC: 55883 AN: 67958

Other (OTH) AF: 0.718 AC: 1517 AN: 2114

Alfa AF: 0.774 Hom.: 156975

Bravo AF: 0.694

TwinsUK AF: 0.807 AC: 2991

ALSPAC AF: 0.819 AC: 3155

ESP6500AA AF: 0.570 AC: 2512

ESP6500EA AF: 0.814 AC: 7002

ExAC AF: 0.715 AC: 86783

Asia WGS AF: 0.533 AC: 1853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.34	T;T
MetaRNN	Benign	7.8e-7	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.88	L;.
PhyloP100		0.14
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.064
Sift	Benign	0.13	T;T
Sift4G	Uncertain	0.012	D;D
Polyphen		0.94	P;.
Vest4		0.023
MPC		0.28
ClinPred		0.021	T
GERP RS		1.2
Varity_R		0.12
gMVP		0.0040
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: rs958305; hg19: chr19-38189440; COSMIC: COSV62206375; COSMIC: COSV62206375;