19-37698716-G-T

Variant names:

• chr19-37698716-G-T
• rs17845437
• NM_032689.5:c.1415C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032689.5(ZNF607):​c.1415C>A​(p.Thr472Lys) 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. 14/22 in silico tools predict 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. T472I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF607 NM_032689.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• Publications: 1 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29554257).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF607	NM_032689.5	c.1415C>A	p.Thr472Lys	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.1415C>A	p.Thr472Lys	missense_variant	Exon 5 of 5	2	NM_032689.5	ENSP00000347338.2
ENSG00000267552	ENST00000586606.6	n.346+1069C>A		intron_variant	Intron 5 of 6	3		ENSP00000467889.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Benign	0.16	T;.
Eigen	Benign	-0.011
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.10	T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L;.
PhyloP100		1.6
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-5.2	D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.25
MutPred		0.54		Gain of methylation at T472 (P = 0.0042);.;
MVP		0.49
MPC		0.20
ClinPred		0.86	D
GERP RS		2.4
Varity_R		0.59
gMVP		0.025
Mutation Taster		=88/12	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: rs17845437; hg19: chr19-38189617;