19-21971191-C-G

Position:

• chr19-21971191-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM4

The NM_007153.3(ZNF208):​c.3843G>C​(p.Ter1281TyrextTer158) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00239 in 115,924 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 not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000073 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF208 NM_007153.3 stop_lost
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.518

Genes affected

ZNF208 (HGNC:12999): (zinc finger protein 208) Zinc finger proteins (ZNFs), such as ZNF208, bind DNA and, through this binding, regulate gene transcription. Most ZNFs contain conserved C2H2 motifs and are classified as Kruppel-type zinc fingers. A conserved protein motif, termed the Kruppel-associated box (KRAB) domain, mediates protein-protein interactions (Eichler et al., 1998 [PubMed 9724325]). See ZNF91 (MIM 603971) for further information on ZNFs.[supplied by OMIM, Aug 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM4: Stoplost variant in NM_007153.3 Downstream stopcodon found after 15 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF208	NM_007153.3	c.3843G>C	p.Ter1281TyrextTer158	stop_lost	4/4	ENST00000397126.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF208	ENST00000397126.9	c.3843G>C	p.Ter1281TyrextTer158	stop_lost	4/4	3	NM_007153.3	P1
ZNF208	ENST00000599916.5	c.305+3538G>C		intron_variant		1
ZNF208	ENST00000601773.5	c.226+16025G>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00240 AC: 278 AN: 115836 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00257

Gnomad AMI AF: 0.00475

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.000729

Gnomad EAS AF: 0.00671

Gnomad SAS AF: 0.00278

Gnomad FIN AF: 0.00503

Gnomad MID AF: 0.0435

Gnomad NFE AF: 0.00181

Gnomad OTH AF: 0.00253

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000732 AC: 103 AN: 1407888 Hom.: 0 Cov.: 124 AF XY: 0.0000672 AC XY: 47 AN XY: 699704

Gnomad4 AFR exome AF: 0.0000318

Gnomad4 AMR exome AF: 0.0000764

Gnomad4 ASJ exome AF: 0.0000819

Gnomad4 EAS exome AF: 0.00206

Gnomad4 SAS exome AF: 0.0000636

Gnomad4 FIN exome AF: 0.0000194

Gnomad4 NFE exome AF: 0.0000148

Gnomad4 OTH exome AF: 0.0000173

GnomAD4 genome AF: 0.00239 AC: 277 AN: 115924 Hom.: 0 Cov.: 31 AF XY: 0.00238 AC XY: 137 AN XY: 57612

Gnomad4 AFR AF: 0.00256

Gnomad4 AMR AF: 0.00135

Gnomad4 ASJ AF: 0.000729

Gnomad4 EAS AF: 0.00647

Gnomad4 SAS AF: 0.00280

Gnomad4 FIN AF: 0.00503

Gnomad4 NFE AF: 0.00181

Gnomad4 OTH AF: 0.00250

Alfa AF: 0.00700 Hom.: 0

ExAC AF: 0.00000827 AC: 1

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

CIC-rearranged sarcoma Other:1

not provided, no classification provided

literature only

Children's Cancer Therapy Development Institute

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.085
DANN	Benign	0.33
Eigen	Benign	-0.78
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.000070	N
MutationTaster	Benign	1.0	N
Vest4		0.0020
GERP RS		-5.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs747779872; hg19: chr19-22153993; COSMIC: COSV68102070; COSMIC: COSV68102070;