rs958305

chr19-37698539-T-Achr19-37698539-T-Cchr19-37698539-T-G

Variant summary

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

The NM_032689.5(ZNF607):c.1592A>T(p.Lys531Ile) 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. 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. K531R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZNF607 NM_032689.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140

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]

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=0.20669916).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF607	NM_032689.5	c.1592A>T	p.Lys531Ile	missense_variant	5/5	ENST00000355202.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF607	ENST00000355202.9	c.1592A>T	p.Lys531Ile	missense_variant	5/5	2	NM_032689.5
ZNF607	ENST00000395835.7	c.1589A>T	p.Lys530Ile	missense_variant	5/5	2		P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 75

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Benign	0.19	T;.
Eigen	Benign	-0.055
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.43	T;T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.8	M;.
MutationTaster	Benign	0.92	P;P
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-7.6	D;D
REVEL	Benign	0.060
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.31
MutPred		0.46		Loss of methylation at K531 (P = 0.0015);.;
MVP		0.42
MPC		0.42
ClinPred		0.99	D
GERP RS		1.2
Varity_R		0.65
gMVP		0.019

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: rs958305; hg19: chr19-38189440;