rs368204022

Variant names:

• chr19-57633350-C-T
• rs368204022
• NM_006385.5:c.4C>T

Variant summary

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

The NM_006385.5(ZNF211):​c.4C>T​(p.Leu2Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000277 in 1,589,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: ZNF211 NM_006385.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0940
• Publications: 0 publications found

Genes affected

ZNF211 (HGNC:13003): (zinc finger protein 211) This gene encodes a protein containing a Kruppel-associated box domain and multiple zinc finger domains. This protein may play a role in developmental processes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

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=0.09848356).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006385.5. 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
	ZNF211	NM_006385.5	MANE Select	c.4C>T	p.Leu2Phe	missense	Exon 1 of 4	NP_006376.2
	ZNF211	NM_001265597.3		c.4C>T	p.Leu2Phe	missense	Exon 1 of 5	NP_001252526.1	Q13398-8
	ZNF211	NM_001322306.2		c.4C>T	p.Leu2Phe	missense	Exon 1 of 5	NP_001309235.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF211	ENST00000240731.5	TSL:2 MANE Select	c.4C>T	p.Leu2Phe	missense	Exon 1 of 4	ENSP00000240731.4	Q13398-7
	ZNF211	ENST00000347302.7	TSL:1	c.4C>T	p.Leu2Phe	missense	Exon 1 of 3	ENSP00000339562.3	Q13398-1
	ZNF211	ENST00000407202.6	TSL:1	c.100-1279C>T		intron	N/A	ENSP00000384436.2	H0Y3T8

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000987 AC: 2 AN: 202654 AF XY: 0.00000897

Gnomad AFR exome AF: 0.00

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: 0.0000112

Gnomad OTH exome AF: 0.000196

GnomAD4 exome AF: 0.0000285 AC: 41 AN: 1437488 Hom.: 0 Cov.: 32 AF XY: 0.0000308 AC XY: 22 AN XY: 713178

African (AFR) AF: 0.00 AC: 0 AN: 33232

American (AMR) AF: 0.0000240 AC: 1 AN: 41710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25516

East Asian (EAS) AF: 0.00 AC: 0 AN: 38942

South Asian (SAS) AF: 0.00 AC: 0 AN: 82842

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46760

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5488

European-Non Finnish (NFE) AF: 0.0000344 AC: 38 AN: 1103482

Other (OTH) AF: 0.0000336 AC: 2 AN: 59516

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152168 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74328

African (AFR) AF: 0.00 AC: 0 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000119 AC: 1

ExAC AF: 0.00000835 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	0.097
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.5
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0036	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.094
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.17	N
REVEL	Benign	0.068
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.086	T
Polyphen		0.70	P
Vest4		0.10
MVP		0.25
MPC		0.36
ClinPred		0.36	T
GERP RS		2.1
PromoterAI		0.18	Neutral
Varity_R		0.099
gMVP		0.14
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

dbSNP: rs368204022; hg19: chr19-58144718;