chr19-36719332-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 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
• Publications: 3 publications found

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

Our verdict: Likely_benign. The variant received -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 VariationId is 2402438.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001322917.1. 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
	ZNF567	NM_001322917.1	MANE Select	c.608C>T	p.Thr203Met	missense	Exon 6 of 6	NP_001309846.1	Q8N184-3
	ZNF567	NM_001387759.1		c.677C>T	p.Thr226Met	missense	Exon 7 of 7	NP_001374688.1
	ZNF567	NM_001300979.2		c.608C>T	p.Thr203Met	missense	Exon 6 of 6	NP_001287908.1	Q8N184-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF567	ENST00000682579.1	MANE Select	c.608C>T	p.Thr203Met	missense	Exon 6 of 6	ENSP00000507048.1	Q8N184-3
	ZNF567	ENST00000360729.8	TSL:1	c.515C>T	p.Thr172Met	missense	Exon 4 of 4	ENSP00000353957.3	Q8N184-1
	ZNF567	ENST00000585696.5	TSL:1	c.515C>T	p.Thr172Met	missense	Exon 3 of 3	ENSP00000467379.1	Q8N184-1

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

GnomAD2 exomes AF: 0.000218 AC: 54 AN: 248130 AF XY: 0.000208

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 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

African (AFR) AF: 0.000659 AC: 22 AN: 33382

American (AMR) AF: 0.0000903 AC: 4 AN: 44310

Ashkenazi Jewish (ASJ) AF: 0.00161 AC: 42 AN: 26078

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39676

South Asian (SAS) AF: 0.000431 AC: 37 AN: 85812

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53392

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1111652

Other (OTH) AF: 0.000265 AC: 16 AN: 60324

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

African (AFR) AF: 0.000361 AC: 15 AN: 41494

American (AMR) AF: 0.000393 AC: 6 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3466

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

South Asian (SAS) AF: 0.000624 AC: 3 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10540

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2112

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

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	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
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-1.4
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.55	N
REVEL	Benign	0.021
Sift	Benign	0.29	T
Sift4G	Benign	0.091	T
Polyphen		0.0	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
Mutation Taster		=99/1	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: rs370163168; hg19: chr19-37210234; COSMIC: COSV62444025;