19-56664306-C-A

Variant names:

• chr19-56664306-C-A
• NM_001005850.3:c.893G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001005850.3(ZNF835):​c.893G>T​(p.Arg298Leu) 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: 35)
• Consequence: ZNF835 NM_001005850.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.158
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18394199).

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.893G>T	p.Arg298Leu	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.893G>T	p.Arg298Leu	missense	Exon 2 of 2	ENSP00000444747.1	Q9Y2P0
	ZNF835	ENST00000890488.1		c.893G>T	p.Arg298Leu	missense	Exon 2 of 2	ENSP00000560547.1
	ZNF835	ENST00000890489.1		c.893G>T	p.Arg298Leu	missense	Exon 2 of 2	ENSP00000560548.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 80

GnomAD4 genome Cov.: 35

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	Uncertain	0.55
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.063	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.16
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Benign	0.028
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0010	D
Vest4		0.26
MVP		0.19
ClinPred		0.97	D
GERP RS		2.1
Varity_R		0.51
gMVP		0.053
Mutation Taster		=95/5	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

hg19: chr19-57175674;