chr9-127428907-C-T

Variant names:

• chr9-127428907-C-T
• rs13292096
• NM_007135.3:c.92C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007135.3(ZNF79):​c.92C>T​(p.Thr31Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 1,592,550 control chromosomes in the GnomAD database, including 276,280 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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: 𝑓 0.61 (28264 hom., cov: 32)
  • Exomes 𝑓: 0.58 (248016 hom.)
• Consequence: ZNF79 NM_007135.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320
• Publications: 54 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0499531E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF79	NM_007135.3	c.92C>T	p.Thr31Ile	missense_variant	Exon 2 of 5	ENST00000342483.5	NP_009066.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF79	ENST00000342483.5	c.92C>T	p.Thr31Ile	missense_variant	Exon 2 of 5	1	NM_007135.3	ENSP00000362446.4

Frequencies

GnomAD3 genomes AF: 0.606 AC: 92062 AN: 151976 Hom.: 28222 Cov.: 32

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.609

GnomAD2 exomes AF: 0.589 AC: 138547 AN: 235334 AF XY: 0.583

Gnomad AFR exome AF: 0.632

Gnomad AMR exome AF: 0.677

Gnomad ASJ exome AF: 0.549

Gnomad EAS exome AF: 0.383

Gnomad FIN exome AF: 0.678

Gnomad NFE exome AF: 0.593

Gnomad OTH exome AF: 0.600

GnomAD4 exome AF: 0.584 AC: 840967 AN: 1440456 Hom.: 248016 Cov.: 33 AF XY: 0.582 AC XY: 416974 AN XY: 716466

African (AFR) AF: 0.641 AC: 20847 AN: 32504

American (AMR) AF: 0.670 AC: 28782 AN: 42960

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 13983 AN: 25618

East Asian (EAS) AF: 0.386 AC: 14767 AN: 38264

South Asian (SAS) AF: 0.524 AC: 43632 AN: 83298

European-Finnish (FIN) AF: 0.675 AC: 35648 AN: 52838

Middle Eastern (MID) AF: 0.590 AC: 3355 AN: 5686

European-Non Finnish (NFE) AF: 0.587 AC: 645812 AN: 1099876

Other (OTH) AF: 0.575 AC: 34141 AN: 59412

GnomAD4 genome AF: 0.606 AC: 92157 AN: 152094 Hom.: 28264 Cov.: 32 AF XY: 0.606 AC XY: 45064 AN XY: 74384

African (AFR) AF: 0.633 AC: 26256 AN: 41466

American (AMR) AF: 0.628 AC: 9604 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1925 AN: 3470

East Asian (EAS) AF: 0.397 AC: 2058 AN: 5178

South Asian (SAS) AF: 0.495 AC: 2383 AN: 4814

European-Finnish (FIN) AF: 0.686 AC: 7259 AN: 10586

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.600 AC: 40785 AN: 67968

Other (OTH) AF: 0.607 AC: 1281 AN: 2112

Alfa AF: 0.596 Hom.: 91656

Bravo AF: 0.604

TwinsUK AF: 0.584 AC: 2166

ALSPAC AF: 0.567 AC: 2185

ESP6500AA AF: 0.640 AC: 2822

ESP6500EA AF: 0.588 AC: 5061

ExAC AF: 0.585 AC: 71041

Asia WGS AF: 0.482 AC: 1673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	T;T;T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.13	.;T;T
MetaRNN	Benign	0.000010	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	.;.;M
PhyloP100		0.032
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.97	.;N;N
REVEL	Benign	0.11
Sift	Benign	0.20	.;T;T
Sift4G	Benign	0.26	T;T;T
Polyphen		0.0010	.;.;B
Vest4		0.036
MPC		0.14
ClinPred		0.011	T
GERP RS		1.9
Varity_R		0.051
gMVP		0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs13292096; hg19: chr9-130191186; COSMIC: COSV61071849;