chr19-53407731-C-T

Variant names:

• chr19-53407731-C-T
• rs566063134
• NM_001040185.3:c.176C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001040185.3(ZNF765):​c.176C>T​(p.Ser59Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,567,872 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: ZNF765 NM_001040185.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.11
• Publications: 3 publications found

Genes affected

ZNF765 (HGNC:25092): (zinc finger protein 765) Predicted to enable DNA-binding transcription factor 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]

ZNF765-ZNF761 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.069061995).
• BP6: Variant 19-53407731-C-T is Benign according to our data. Variant chr19-53407731-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3478253.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040185.3. 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
	ZNF765	NM_001040185.3	MANE Select	c.176C>T	p.Ser59Leu	missense	Exon 4 of 4	NP_001035275.1	Q7L2R6-1
	ZNF765	NM_001350495.2		c.17C>T	p.Ser6Leu	missense	Exon 3 of 3	NP_001337424.1
	ZNF765-ZNF761	NM_001350496.2		c.-1345+5540C>T		intron	N/A	NP_001337425.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF765	ENST00000396408.8	TSL:1 MANE Select	c.176C>T	p.Ser59Leu	missense	Exon 4 of 4	ENSP00000379689.3	Q7L2R6-1
	ZNF765	ENST00000504235.5	TSL:1	n.142+5540C>T		intron	N/A	ENSP00000424395.1	Q7L2R6-2
	ZNF765	ENST00000933978.1		c.176C>T	p.Ser59Leu	missense	Exon 3 of 3	ENSP00000604037.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152128 Hom.: 0 Cov.: 33

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: 0.00000465 AC: 1 AN: 214878 AF XY: 0.00

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: 0.00000990

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000226 AC: 32 AN: 1415626 Hom.: 0 Cov.: 30 AF XY: 0.0000171 AC XY: 12 AN XY: 700394

African (AFR) AF: 0.00 AC: 0 AN: 31708

American (AMR) AF: 0.00 AC: 0 AN: 36344

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23296

East Asian (EAS) AF: 0.00 AC: 0 AN: 39302

South Asian (SAS) AF: 0.00 AC: 0 AN: 77898

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51864

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5520

European-Non Finnish (NFE) AF: 0.0000293 AC: 32 AN: 1091368

Other (OTH) AF: 0.00 AC: 0 AN: 58326

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152246 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74444

African (AFR) AF: 0.0000241 AC: 1 AN: 41532

American (AMR) AF: 0.00 AC: 0 AN: 15292

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.069
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.0050
DANN	Benign	0.25
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00093	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.48	N
PhyloP100		-5.1
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.018
Sift	Benign	0.64	T
Sift4G	Benign	0.73	T
Polyphen		0.0040	B
Vest4		0.078
MVP		0.13
MPC		0.043
ClinPred		0.017	T
GERP RS		-2.0
Varity_R		0.033
gMVP		0.011
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs566063134; hg19: chr19-53910984; COSMIC: COSV67182606;