9-127428858-C-T

Variant names:

• chr9-127428858-C-T
• NM_007135.3:c.43C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007135.3(ZNF79):​c.43C>T​(p.Pro15Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF79 NM_007135.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.715

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

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=0.033895522).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF79	NM_007135.3	c.43C>T	p.Pro15Ser	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.43C>T	p.Pro15Ser	missense_variant	Exon 2 of 5	1	NM_007135.3	ENSP00000362446.4
ZNF79	ENST00000543471	c.-30C>T		5_prime_UTR_variant	Exon 3 of 6	2		ENSP00000438418.1
ZNF79	ENST00000612342	c.-30C>T		5_prime_UTR_variant	Exon 2 of 5	2		ENSP00000478201.1
ZNF79	ENST00000617266	c.-137C>T		5_prime_UTR_variant	Exon 2 of 3	3		ENSP00000484833.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.43C>T (p.P15S) 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 43, causing the proline (P) at amino acid position 15 to be replaced by a serine (S). 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	0.080
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.43
DANN	Benign	0.23
DEOGEN2	Benign	0.093	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0081	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.71	N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.42	N
REVEL	Benign	0.072
Sift	Benign	0.92	T
Sift4G	Benign	0.28	T
Polyphen		0.0010	B
Vest4		0.050
MutPred		0.21		Gain of phosphorylation at P15 (P = 0.0325);
MVP		0.14
MPC		0.12
ClinPred		0.014	T
GERP RS		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.015
gMVP		0.19

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.

Other links and lift over

hg19: chr9-130191137;