19-37698539-T-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032689.5(ZNF607):​c.1592A>C​(p.Lys531Thr) 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.

• Frequency: Genomes: not found (cov: 31)
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17009869).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF607	NM_032689.5	c.1592A>C	p.Lys531Thr	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>C	p.Lys531Thr	missense_variant	Exon 5 of 5	2	NM_032689.5	ENSP00000347338.2
ENSG00000267552	ENST00000586606.6	n.346+1246A>C		intron_variant	Intron 5 of 6	3		ENSP00000467889.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 75

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 156975

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.45	T;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.3	M;.
PhyloP100		0.14
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-5.7	D;D
REVEL	Benign	0.053
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.20
MutPred		0.47		Loss of methylation at K531 (P = 0.0015);.;
MVP		0.40
MPC		0.36
ClinPred		0.98	D
GERP RS		1.2
Varity_R		0.43
gMVP		0.014
Mutation Taster		=96/4	polymorphism

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;