11-3359551-C-T

Variant names:

• chr11-3359551-C-T
• rs372904601
• NM_001130520.3:c.1457G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001130520.3(ZNF195):​c.1457G>A​(p.Arg486Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,613,910 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R486I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: ZNF195 NM_001130520.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.030091405).

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.1457G>A	p.Arg486Lys	missense	Exon 6 of 6	NP_001123992.1	O14628-1
	ZNF195	NM_001242841.2		c.1400G>A	p.Arg467Lys	missense	Exon 6 of 6	NP_001229770.1	O14628-6
	ZNF195	NM_001130519.3		c.1388G>A	p.Arg463Lys	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.1457G>A	p.Arg486Lys	missense	Exon 6 of 6	ENSP00000382511.4	O14628-1
	ZNF195	ENST00000005082.13	TSL:1	c.1388G>A	p.Arg463Lys	missense	Exon 5 of 5	ENSP00000005082.9	O14628-5
	ZNF195	ENST00000354599.10	TSL:1	c.1241G>A	p.Arg414Lys	missense	Exon 4 of 4	ENSP00000346613.6	O14628-4

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 152036 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

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: 0.0000441 AC: 11 AN: 249608 AF XY: 0.0000295

Gnomad AFR exome AF: 0.000387

Gnomad AMR exome AF: 0.000145

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: 0.0000157 AC: 23 AN: 1461874 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727236

African (AFR) AF: 0.000538 AC: 18 AN: 33480

American (AMR) AF: 0.000112 AC: 5 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.000191 AC: 29 AN: 152036 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74258

African (AFR) AF: 0.000507 AC: 21 AN: 41388

American (AMR) AF: 0.000524 AC: 8 AN: 15276

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67990

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000287 Hom.: 1

Bravo AF: 0.000159

ESP6500AA AF: 0.000488 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000248 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.8
DANN	Benign	0.93
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.00013	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.095	N
PhyloP100		0.12
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.066
Sift	Benign	0.31	T
Sift4G	Benign	0.18	T
Polyphen		0.78	P
Vest4		0.076
MVP		0.33
MPC		0.56
ClinPred		0.042	T
GERP RS		1.3
Varity_R		0.084
gMVP		0.041
Mutation Taster		=94/6	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: rs372904601; hg19: chr11-3380781; COSMIC: COSV99137989; COSMIC: COSV99137989;