19-57634049-C-G

Variant names:

• chr19-57634049-C-G
• rs940986385
• NM_006385.5:c.117C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001265599.3(ZNF211):​c.-106C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000247 in 1,581,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: ZNF211 NM_001265599.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.304
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043961465).
• BP6: Variant 19-57634049-C-G is Benign according to our data. Variant chr19-57634049-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3335136.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001265599.3. 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
	ZNF211	NM_006385.5	MANE Select	c.117C>G	p.Phe39Leu	missense	Exon 2 of 4	NP_006376.2
	ZNF211	NM_001265599.3		c.-106C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	NP_001252528.1	Q13398-2
	ZNF211	NM_001265597.3		c.117C>G	p.Phe39Leu	missense	Exon 2 of 5	NP_001252526.1	Q13398-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF211	ENST00000240731.5	TSL:2 MANE Select	c.117C>G	p.Phe39Leu	missense	Exon 2 of 4	ENSP00000240731.4	Q13398-7
	ZNF211	ENST00000407202.6	TSL:1	c.100-580C>G		intron	N/A	ENSP00000384436.2	H0Y3T8
	ZNF211	ENST00000347302.7	TSL:1	c.91-580C>G		intron	N/A	ENSP00000339562.3	Q13398-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152174 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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000138 AC: 3 AN: 217742 AF XY: 0.0000171

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: 0.0000200

Gnomad OTH exome AF: 0.000195

GnomAD4 exome AF: 0.0000266 AC: 38 AN: 1429636 Hom.: 0 Cov.: 31 AF XY: 0.0000310 AC XY: 22 AN XY: 709452

African (AFR) AF: 0.00 AC: 0 AN: 32368

American (AMR) AF: 0.00 AC: 0 AN: 39204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23194

East Asian (EAS) AF: 0.00 AC: 0 AN: 39616

South Asian (SAS) AF: 0.00 AC: 0 AN: 80562

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51930

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5554

European-Non Finnish (NFE) AF: 0.0000346 AC: 38 AN: 1098274

Other (OTH) AF: 0.00 AC: 0 AN: 58934

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74336

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15274

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Likely benign

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	Pathogenic	0.58
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.89
DANN	Benign	0.43
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00026	N
LIST_S2	Benign	0.037	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-0.91	T
PhyloP100		-0.30
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.11	N
REVEL	Benign	0.0090
Sift	Benign	0.80	T
Sift4G	Benign	0.69	T
Vest4		0.081
MVP		0.014
MPC		0.098
ClinPred		0.027	T
GERP RS		-2.7
gMVP		0.19
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs940986385; hg19: chr19-58145417;