9-127435980-A-C

Variant names:

• chr9-127435980-A-C
• NM_007135.3:c.305A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007135.3(ZNF79):​c.305A>C​(p.Glu102Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E102K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: ZNF79 NM_007135.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.04
• Publications: 0 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: 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=0.0858573).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007135.3. 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
	ZNF79	NM_007135.3	MANE Select	c.305A>C	p.Glu102Ala	missense	Exon 4 of 5	NP_009066.2	Q15937
	ZNF79	NM_001286696.2		c.233A>C	p.Glu78Ala	missense	Exon 4 of 5	NP_001273625.1	F5H032
	ZNF79	NM_001286697.2		c.233A>C	p.Glu78Ala	missense	Exon 5 of 6	NP_001273626.1	F5H032

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF79	ENST00000342483.5	TSL:1 MANE Select	c.305A>C	p.Glu102Ala	missense	Exon 4 of 5	ENSP00000362446.4	Q15937
	ZNF79	ENST00000543471.6	TSL:2	c.233A>C	p.Glu78Ala	missense	Exon 5 of 6	ENSP00000438418.1	F5H032
	ZNF79	ENST00000850856.1		c.233A>C	p.Glu78Ala	missense	Exon 4 of 5	ENSP00000520944.1	F5H032

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.11
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.94
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.0
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.026
Sift	Benign	0.24	T
Sift4G	Uncertain	0.060	T
Polyphen		0.020	B
Vest4		0.24
MutPred		0.15		Gain of helix (P = 0.1736)
MVP		0.26
MPC		0.13
ClinPred		0.043	T
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.050
gMVP		0.065
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

hg19: chr9-130198259;