chr19-56664276-C-A

Variant names:

• chr19-56664276-C-A
• rs762463668
• NM_001005850.3:c.923G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001005850.3(ZNF835):​c.923G>T​(p.Cys308Phe) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 35)
• Consequence: ZNF835 NM_001005850.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.02
• Publications: 2 publications found

Genes affected

ZNF835 (HGNC:34332): (zinc finger protein 835) Predicted to enable DNA-binding transcription factor activity 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 located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZIM2-AS1 (HGNC:51304): (ZIM2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.833

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005850.3. 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
	ZNF835	NM_001005850.3	MANE Select	c.923G>T	p.Cys308Phe	missense	Exon 2 of 2	NP_001005850.2	Q9Y2P0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF835	ENST00000537055.4	TSL:2 MANE Select	c.923G>T	p.Cys308Phe	missense	Exon 2 of 2	ENSP00000444747.1	Q9Y2P0
	ZNF835	ENST00000890488.1		c.923G>T	p.Cys308Phe	missense	Exon 2 of 2	ENSP00000560547.1
	ZNF835	ENST00000890489.1		c.923G>T	p.Cys308Phe	missense	Exon 2 of 2	ENSP00000560548.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 81

GnomAD4 genome Cov.: 35

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Pathogenic	0.82
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.42	T
Eigen	Uncertain	0.42
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.051	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	0.74	D
MutationAssessor	Pathogenic	3.8	H
PhyloP100		3.0
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-11	D
REVEL	Uncertain	0.40
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.54
MVP		0.51
ClinPred		1.0	D
GERP RS		2.1
Varity_R		0.86
gMVP		0.12
Mutation Taster		=77/23	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: rs762463668; hg19: chr19-57175644;