11-3360224-G-A

Variant names:

• chr11-3360224-G-A
• rs755929724
• NM_001130520.3:c.784C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001130520.3(ZNF195):​c.784C>T​(p.His262Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,613,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: ZNF195 NM_001130520.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.41
• Publications: 0 publications found

Genes affected

ZNF195 (HGNC:12986): (zinc finger protein 195) This gene encodes a protein belonging to the Krueppel C2H2-type zinc-finger protein family. These family members are transcription factors that are implicated in a variety of cellular processes. This gene is located near the centromeric border of chromosome 11p15.5, next to an imprinted domain that is associated with maternal-specific loss of heterozygosity in Wilms' tumors. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.928

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130520.3. 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
	ZNF195	NM_001130520.3	MANE Select	c.784C>T	p.His262Tyr	missense	Exon 6 of 6	NP_001123992.1	O14628-1
	ZNF195	NM_001242841.2		c.727C>T	p.His243Tyr	missense	Exon 6 of 6	NP_001229770.1	O14628-6
	ZNF195	NM_001130519.3		c.715C>T	p.His239Tyr	missense	Exon 5 of 5	NP_001123991.1	O14628-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF195	ENST00000399602.9	TSL:1 MANE Select	c.784C>T	p.His262Tyr	missense	Exon 6 of 6	ENSP00000382511.4	O14628-1
	ZNF195	ENST00000005082.13	TSL:1	c.715C>T	p.His239Tyr	missense	Exon 5 of 5	ENSP00000005082.9	O14628-5
	ZNF195	ENST00000354599.10	TSL:1	c.568C>T	p.His190Tyr	missense	Exon 4 of 4	ENSP00000346613.6	O14628-4

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152070 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1461754 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10 AN XY: 727170

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1111986

Other (OTH) AF: 0.0000166 AC: 1 AN: 60388

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152070 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74286

African (AFR) AF: 0.0000242 AC: 1 AN: 41386

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000565 Hom.: 0

Bravo AF: 0.0000113

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

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	0.34
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.016
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0076	T
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	0.11	D
MutationAssessor	Pathogenic	3.7	H
PhyloP100		4.4
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Uncertain	0.45
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.012	D
Polyphen		0.99	D
Vest4		0.20
MutPred		0.78		Loss of disorder (P = 0.0384)
MVP		0.88
MPC		0.86
ClinPred		0.94	D
GERP RS		0.076
Varity_R		0.29
gMVP		0.19
Mutation Taster		=93/7	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: rs755929724; hg19: chr11-3381454;