19-56663659-C-T

Variant names:

• chr19-56663659-C-T
• rs544966993
• NM_001005850.3:c.1540G>A

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.1540G>A​(p.Gly514Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF835 NM_001005850.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17
• 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=0.07731432).

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.1540G>A	p.Gly514Arg	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.1540G>A	p.Gly514Arg	missense	Exon 2 of 2	ENSP00000444747.1	Q9Y2P0
	ZNF835	ENST00000890488.1		c.1540G>A	p.Gly514Arg	missense	Exon 2 of 2	ENSP00000560547.1
	ZNF835	ENST00000890489.1		c.1540G>A	p.Gly514Arg	missense	Exon 2 of 2	ENSP00000560548.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.8
DANN	Benign	0.91
DEOGEN2	Benign	0.00031	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N
PhyloP100		-2.2
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.050	N
REVEL	Benign	0.010
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0070	D
Vest4		0.058
MVP		0.076
ClinPred		0.13	T
GERP RS		1.1
Varity_R		0.057
gMVP		0.034
Mutation Taster		=99/1	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: rs544966993; hg19: chr19-57175027;