chr19-53237592-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E379A) has been classified 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
• Publications: 0 publications found

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]

ENSG00000291131 (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=0.13474303).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182609.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF677	NM_182609.4	MANE Select	c.1135G>C	p.Glu379Gln	missense	Exon 5 of 5	NP_872415.1	Q86XU0
	ZNF677	NM_001317998.2		c.1135G>C	p.Glu379Gln	missense	Exon 5 of 5	NP_001304927.1	Q86XU0
	ZNF677	NM_001385608.1		c.1135G>C	p.Glu379Gln	missense	Exon 5 of 5	NP_001372537.1	Q86XU0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF677	ENST00000598513.6	TSL:1 MANE Select	c.1135G>C	p.Glu379Gln	missense	Exon 5 of 5	ENSP00000469391.1	Q86XU0
	ZNF677	ENST00000333952.8	TSL:2	c.1135G>C	p.Glu379Gln	missense	Exon 3 of 3	ENSP00000334394.4	Q86XU0
	ZNF677	ENST00000881288.1		c.1135G>C	p.Glu379Gln	missense	Exon 5 of 5	ENSP00000551347.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 57

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.25	N
PhyloP100		-1.3
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.062
Sift	Benign	0.062	T
Sift4G	Uncertain	0.052	T
Polyphen		0.95	P
Vest4		0.10
MutPred		0.50		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
Mutation Taster		=100/0	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: rs773041798; hg19: chr19-53740845;