19-53237592-C-G

Variant names:

• chr19-53237592-C-G
• rs773041798
• NM_182609.4:c.1135G>C

Variant summary

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

The NM_182609.4(ZNF677):​c.1135G>C​(p.Glu379Gln) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF677 NM_182609.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.26

Genes affected

ZNF677 (HGNC:28730): (zinc finger protein 677) 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=0.13474303).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF677	NM_182609.4	c.1135G>C	p.Glu379Gln	missense_variant	Exon 5 of 5	ENST00000598513.6	NP_872415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF677	ENST00000598513.6	c.1135G>C	p.Glu379Gln	missense_variant	Exon 5 of 5	1	NM_182609.4	ENSP00000469391.1
ZNF677	ENST00000333952.8	c.1135G>C	p.Glu379Gln	missense_variant	Exon 3 of 3	2		ENSP00000334394.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 57

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 17, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1135G>C (p.E379Q) alteration is located in exon 5 (coding exon 3) of the ZNF677 gene. This alteration results from a G to C substitution at nucleotide position 1135, causing the glutamic acid (E) at amino acid position 379 to be replaced by a glutamine (Q). 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	Benign	0.19
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	4.5
DANN	Benign	0.95
DEOGEN2	Benign	0.040	T;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.0012	N
LIST_S2	Benign	0.20	.;T
M_CAP	Benign	0.00097	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.25	N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.1	.;N
REVEL	Benign	0.062
Sift	Benign	0.062	.;T
Sift4G	Uncertain	0.052	T;T
Polyphen		0.95	P;P
Vest4		0.10
MutPred		0.50		Gain of ubiquitination at K382 (P = 0.0985);Gain of ubiquitination at K382 (P = 0.0985);
MVP		0.45
MPC		0.047
ClinPred		0.17	T
GERP RS		1.1
Varity_R		0.091
gMVP		0.049

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: rs773041798; hg19: chr19-53740845;