9-127444173-C-T

Variant names:

• chr9-127444173-C-T
• rs1397308410
• NM_007135.3:c.473C>T

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.473C>T​(p.Ser158Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S158C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF79 NM_007135.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.857
• 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=0.078602105).

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.473C>T	p.Ser158Phe	missense	Exon 5 of 5	NP_009066.2	Q15937
	ZNF79	NM_001286696.2		c.401C>T	p.Ser134Phe	missense	Exon 5 of 5	NP_001273625.1	F5H032
	ZNF79	NM_001286697.2		c.401C>T	p.Ser134Phe	missense	Exon 6 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.473C>T	p.Ser158Phe	missense	Exon 5 of 5	ENSP00000362446.4	Q15937
	ZNF79	ENST00000543471.6	TSL:2	c.401C>T	p.Ser134Phe	missense	Exon 6 of 6	ENSP00000438418.1	F5H032
	ZNF79	ENST00000850856.1		c.401C>T	p.Ser134Phe	missense	Exon 5 of 5	ENSP00000520944.1	F5H032

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461734 Hom.: 0 Cov.: 51 AF XY: 0.00 AC XY: 0 AN XY: 727172

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60392

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	11
DANN	Benign	0.81
DEOGEN2	Benign	0.048	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.041	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.86
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.080
Sift	Benign	0.71	T
Sift4G	Benign	0.68	T
Polyphen		0.70	P
Vest4		0.24
MutPred		0.29		Loss of phosphorylation at S158 (P = 0.1315)
MVP		0.37
MPC		0.47
ClinPred		0.21	T
GERP RS		3.0
Varity_R		0.080
gMVP		0.10
Mutation Taster		=95/5	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

dbSNP: rs1397308410; hg19: chr9-130206452; COSMIC: COSV106477143; COSMIC: COSV106477143;