Variant 16-30525515-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024671.4(ZNF768):c.625G>A(p.Asp209Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,832 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZNF768
NM_024671.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.490

Variant links:

Genes affected

ZNF768 (HGNC:26273): (zinc finger protein 768) Enables RNA 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]

ZNF768 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06412673).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF768	NM_024671.4 linkuse as main transcript	c.625G>A	p.Asp209Asn	missense_variant	2/2	ENST00000380412.7	NP_078947.3	Q9H5H4A0A024QZC8
ZNF768	XM_017023665.3 linkuse as main transcript	c.697G>A	p.Asp233Asn	missense_variant	2/2		XP_016879154.1
ZNF768	XM_017023666.2 linkuse as main transcript	c.532G>A	p.Asp178Asn	missense_variant	2/2		XP_016879155.1	H3BS42

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF768	ENST00000380412.7 linkuse as main transcript	c.625G>A	p.Asp209Asn	missense_variant	2/2	1	NM_024671.4	ENSP00000369777.5		Q9H5H4
ZNF768	ENST00000562803.1 linkuse as main transcript	c.532G>A	p.Asp178Asn	missense_variant	2/2	3		ENSP00000456527.1		H3BS42

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461832

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 10, 2024

The c.625G>A (p.D209N) alteration is located in exon 2 (coding exon 2) of the ZNF768 gene. This alteration results from a G to A substitution at nucleotide position 625, causing the aspartic acid (D) at amino acid position 209 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0080

T;.

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.0085

MetaRNN

Benign

0.064

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;.

PrimateAI

Benign

0.32

PROVEAN

Benign

0.14

N;.

REVEL

Benign

0.17

Sift

Benign

1.0

T;.

Sift4G

Benign

0.54

T;T

Polyphen

0.0040

B;.

Vest4

0.043

MutPred

0.47

Gain of catalytic residue at D209 (P = 0.1081);.;

MVP

0.12

MPC

0.69

ClinPred

0.16

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.069

gMVP

0.24

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over