Genetic Variant NM_001351774.2:c.76G>C (chr19-52888193-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001351774.2(ZNF320):c.76G>C(p.Asp26His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000763 in 1,532,968 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000043 ( 0 hom., cov: 21)

Exomes 𝑓: 0.000080 ( 0 hom. )

Consequence

ZNF320
NM_001351774.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.762

Publications

1 publications found

Variant links:

Genes affected

ZNF320 (HGNC:13842): (zinc finger protein 320) ZNF320 encodes a Kruppel-like zinc finger protein. Members of this protein family are involved in activation or repression of transcription.[supplied by OMIM, Jul 2002]

ZNF320 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1522325).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF320	NM_001351774.2 link	c.76G>C	p.Asp26His	missense_variant	Exon 5 of 6	ENST00000682928.1	NP_001338703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF320	ENST00000682928.1 link	c.76G>C	p.Asp26His	missense_variant	Exon 5 of 6		NM_001351774.2	ENSP00000506814.1		A2RRD8

Frequencies

GnomAD3 genomes

AF:

0.0000500

AC:

AN:

140010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000536

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000145

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:

0.0000466

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000295

AC:

AN:

203602

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000804

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000205

Gnomad OTH exome

AF:

0.000419

GnomAD4 exome

AF:

0.0000797

AC:

111

AN:

1392844

Hom.:

Cov.:

AF XY:

0.0000782

AC XY:

AN XY:

690430

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30940

American (AMR)

AF:

0.0000281

AC:

AN:

35546

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22970

East Asian (EAS)

AF:

0.00

AC:

AN:

39238

South Asian (SAS)

AF:

0.00

AC:

AN:

78728

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48472

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5424

European-Non Finnish (NFE)

AF:

0.0000978

AC:

105

AN:

1074032

Other (OTH)

AF:

0.0000870

AC:

AN:

57494

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000428

AC:

AN:

140124

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

67688

show subpopulations

African (AFR)

AF:

0.0000535

AC:

AN:

37396

American (AMR)

AF:

0.000145

AC:

AN:

13770

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3334

East Asian (EAS)

AF:

0.00

AC:

AN:

4884

South Asian (SAS)

AF:

0.00

AC:

AN:

4078

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9286

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000311

AC:

AN:

64352

Other (OTH)

AF:

0.00

AC:

AN:

1866

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000498

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 05, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.76G>C (p.D26H) alteration is located in exon 3 (coding exon 2) of the ZNF320 gene. This alteration results from a G to C substitution at nucleotide position 76, causing the aspartic acid (D) at amino acid position 26 to be replaced by a histidine (H). 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

Uncertain

0.51

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

.;T;.;.;.;.;.

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.0031

LIST_S2

Benign

0.057

T;.;T;T;T;T;.

M_CAP

Benign

0.0016

MetaRNN

Benign

0.15

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.0

.;M;.;.;.;.;.

PhyloP100

-0.76

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-2.8

D;.;.;.;.;.;.

REVEL

Benign

0.056

Sift

Uncertain

0.013

D;.;.;.;.;.;.

Sift4G

Uncertain

0.0040

D;D;.;.;D;.;.

Polyphen

0.99

.;D;.;.;.;.;.

Vest4

0.26

MutPred

0.54

Gain of helix (P = 0.062);Gain of helix (P = 0.062);Gain of helix (P = 0.062);Gain of helix (P = 0.062);Gain of helix (P = 0.062);Gain of helix (P = 0.062);Gain of helix (P = 0.062);

MVP

0.20

MPC

3.4

ClinPred

0.69

GERP RS

-1.7

Varity_R

0.092

gMVP

0.16

Mutation Taster

=94/6

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over