19-36719332-C-T

Variant names:

• chr19-36719332-C-T
• rs370163168
• NM_001322917.1:c.608C>T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001322917.1(ZNF567):​c.608C>T​(p.Thr203Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,612,484 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000099 (1 hom.)
• Consequence: ZNF567 NM_001322917.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.43

Genes affected

ZNF567 (HGNC:28696): (zinc finger protein 567) Predicted to enable DNA-binding transcription factor activity and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF850 (HGNC:27994): (zinc finger protein 850) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011468172).
• BP6: Variant 19-36719332-C-T is Benign according to our data. Variant chr19-36719332-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2402438.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF567	NM_001322917.1	c.608C>T	p.Thr203Met	missense_variant	Exon 6 of 6	ENST00000682579.1	NP_001309846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF567	ENST00000682579.1	c.608C>T	p.Thr203Met	missense_variant	Exon 6 of 6		NM_001322917.1	ENSP00000507048.1

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 151982 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000363

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000218 AC: 54 AN: 248130 Hom.: 0 AF XY: 0.000208 AC XY: 28 AN XY: 134412

Gnomad AFR exome AF: 0.000881

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.00211

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000366

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.000334

GnomAD4 exome AF: 0.0000986 AC: 144 AN: 1460384 Hom.: 1 Cov.: 33 AF XY: 0.000123 AC XY: 89 AN XY: 726422

Gnomad4 AFR exome AF: 0.000659

Gnomad4 AMR exome AF: 0.0000903

Gnomad4 ASJ exome AF: 0.00161

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000431

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000180

Gnomad4 OTH exome AF: 0.000265

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152100 Hom.: 1 Cov.: 32 AF XY: 0.000229 AC XY: 17 AN XY: 74340

Gnomad4 AFR AF: 0.000361

Gnomad4 AMR AF: 0.000393

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000624

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000115 Hom.: 0

Bravo AF: 0.000227

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000264 AC: 32

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 16, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.0
DANN	Benign	0.79
DEOGEN2	Benign	0.024	T;.;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.000040	N
LIST_S2	Benign	0.050	T;.;T;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.011	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.;.;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.55	N;N;.;.
REVEL	Benign	0.021
Sift	Benign	0.29	T;T;.;.
Sift4G	Benign	0.091	T;T;T;T
Polyphen		0.0	B;.;B;.
Vest4		0.031
MVP		0.32
MPC		0.28
ClinPred		0.0026	T
GERP RS		-0.37
Varity_R		0.016
gMVP		0.21

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: rs370163168; hg19: chr19-37210234; COSMIC: COSV62444025;