19-56664009-G-A

Variant names:

• chr19-56664009-G-A
• rs757263771
• NM_001005850.3:c.1190C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001005850.3(ZNF835):​c.1190C>T​(p.Ala397Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,609,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A397D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF835 NM_001005850.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045218945).

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.1190C>T	p.Ala397Val	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.1190C>T	p.Ala397Val	missense	Exon 2 of 2	ENSP00000444747.1	Q9Y2P0
	ZNF835	ENST00000890488.1		c.1190C>T	p.Ala397Val	missense	Exon 2 of 2	ENSP00000560547.1
	ZNF835	ENST00000890489.1		c.1190C>T	p.Ala397Val	missense	Exon 2 of 2	ENSP00000560548.1

Frequencies

GnomAD3 genomes AF: 0.0000200 AC: 3 AN: 149706 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000741

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000807 AC: 2 AN: 247744 AF XY: 0.00000742

Gnomad AFR exome AF: 0.000130

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460244 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726512

African (AFR) AF: 0.0000299 AC: 1 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111420

Other (OTH) AF: 0.00 AC: 0 AN: 60340

GnomAD4 genome AF: 0.0000200 AC: 3 AN: 149706 Hom.: 0 Cov.: 33 AF XY: 0.0000137 AC XY: 1 AN XY: 73016

African (AFR) AF: 0.0000741 AC: 3 AN: 40502

American (AMR) AF: 0.00 AC: 0 AN: 15060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3452

East Asian (EAS) AF: 0.00 AC: 0 AN: 5042

South Asian (SAS) AF: 0.00 AC: 0 AN: 4732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 298

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67332

Other (OTH) AF: 0.00 AC: 0 AN: 2060

Alfa AF: 0.0000675 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.6
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0077	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.20
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.028
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0070	D
Vest4		0.073
MVP		0.092
ClinPred		0.042	T
GERP RS		-0.40
Varity_R		0.10
gMVP		0.022
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: rs757263771; hg19: chr19-57175377; COSMIC: COSV104440721; COSMIC: COSV104440721;