Genetic Variant NM_007135.3:c.103C>T (chr9-127428918-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007135.3(ZNF79):c.103C>T(p.Arg35Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000255 in 1,574,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

ZNF79
NM_007135.3 missense, splice_region

Scores

Splicing: ADA: 0.9707

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.64

Variant links:

Genes affected

ZNF79 (HGNC:13153): (zinc finger protein 79) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF79 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07652414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF79	NM_007135.3 link	c.103C>T	p.Arg35Trp	missense_variant, splice_region_variant	Exon 2 of 5	ENST00000342483.5	NP_009066.2	Q15937

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF79	ENST00000342483.5 link	c.103C>T	p.Arg35Trp	missense_variant, splice_region_variant	Exon 2 of 5	1	NM_007135.3	ENSP00000362446.4		Q15937

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

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:

0.000279

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000162

AC:

AN:

222644

Hom.:

AF XY:

0.000148

AC XY:

AN XY:

121220

show subpopulations

Gnomad AFR exome

AF:

0.0000700

Gnomad AMR exome

AF:

0.0000353

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000751

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000314

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000264

AC:

376

AN:

1422468

Hom.:

Cov.:

AF XY:

0.000240

AC XY:

170

AN XY:

707166

show subpopulations

Gnomad4 AFR exome

AF:

0.0000635

Gnomad4 AMR exome

AF:

0.0000252

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000266

Gnomad4 SAS exome

AF:

0.0000249

Gnomad4 FIN exome

AF:

0.0000191

Gnomad4 NFE exome

AF:

0.000328

Gnomad4 OTH exome

AF:

0.000188

GnomAD4 genome

AF:

0.000164

AC:

AN:

152284

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000365

Hom.:

Bravo

AF:

0.000155

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000214

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.103C>T (p.R35W) alteration is located in exon 2 (coding exon 2) of the ZNF79 gene. This alteration results from a C to T substitution at nucleotide position 103, causing the arginine (R) at amino acid position 35 to be replaced by a tryptophan (W). 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

0.12

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.082

T;T;T

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.35

.;T;T

M_CAP

Benign

0.0079

MetaRNN

Benign

0.077

T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

0.63

.;.;N

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.6

.;N;N

REVEL

Benign

0.11

Sift

Benign

0.047

.;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.91

.;.;P

Vest4

0.18

MVP

0.61

MPC

0.16

ClinPred

0.072

GERP RS

3.8

Varity_R

0.046

gMVP

0.075

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.97

dbscSNV1_RF

Benign

0.48

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over