NM_032689.5:c.1868G>C

Variant names:

• chr19-37698263-C-G
• NM_032689.5:c.1868G>C

Variant summary

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

The NM_032689.5(ZNF607):​c.1868G>C​(p.Gly623Ala) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF607 NM_032689.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.52

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

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=0.22266167).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF607	NM_032689.5	c.1868G>C	p.Gly623Ala	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.1868G>C	p.Gly623Ala	missense_variant	Exon 5 of 5	2	NM_032689.5	ENSP00000347338.2
ENSG00000267552	ENST00000586606.6	n.346+1522G>C		intron_variant	Intron 5 of 6	3		ENSP00000467889.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1868G>C (p.G623A) alteration is located in exon 5 (coding exon 4) of the ZNF607 gene. This alteration results from a G to C substitution at nucleotide position 1868, causing the glycine (G) at amino acid position 623 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T;.
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.00087	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Benign	0.25	T
PROVEAN	Pathogenic	-4.9	D;D
REVEL	Benign	0.012
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.98	D;.
Vest4		0.12
MutPred		0.57		Gain of catalytic residue at G623 (P = 0.1251);.;
MVP		0.41
MPC		0.31
ClinPred		0.97	D
GERP RS		0.48
Varity_R		0.15
gMVP		0.013

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-38189164;