chr9-127428918-C-T

Variant names:

• chr9-127428918-C-T
• rs200385658
• NM_007135.3:c.103C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001286698.2(ZNF79):​c.-77C>T variant causes a 5 prime UTR premature start codon gain 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. 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_001286698.2 5_prime_UTR_premature_start_codon_gain
• Scores: Splicing: ADA: 0.9707
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.64
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07652414).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286698.2. 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.103C>T	p.Arg35Trp	missense splice_region	Exon 2 of 5	NP_009066.2	Q15937
	ZNF79	NM_001286698.2		c.-77C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 3	NP_001273627.1	A0A087X2B0
	ZNF79	NM_001286696.2		c.31C>T	p.Arg11Trp	missense splice_region	Exon 2 of 5	NP_001273625.1	F5H032

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF79	ENST00000342483.5	TSL:1 MANE Select	c.103C>T	p.Arg35Trp	missense splice_region	Exon 2 of 5	ENSP00000362446.4	Q15937
	ZNF79	ENST00000617266.2	TSL:3	c.-77C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 3	ENSP00000484833.1	A0A087X2B0
	ZNF79	ENST00000543471.6	TSL:2	c.31C>T	p.Arg11Trp	missense splice_region	Exon 3 of 6	ENSP00000438418.1	F5H032

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152166 Hom.: 0 Cov.: 31

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

GnomAD2 exomes AF: 0.000162 AC: 36 AN: 222644 AF XY: 0.000148

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 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.: 0 Cov.: 29 AF XY: 0.000240 AC XY: 170 AN XY: 707166

African (AFR) AF: 0.0000635 AC: 2 AN: 31516

American (AMR) AF: 0.0000252 AC: 1 AN: 39744

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25018

East Asian (EAS) AF: 0.0000266 AC: 1 AN: 37534

South Asian (SAS) AF: 0.0000249 AC: 2 AN: 80456

European-Finnish (FIN) AF: 0.0000191 AC: 1 AN: 52446

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5608

European-Non Finnish (NFE) AF: 0.000328 AC: 358 AN: 1091578

Other (OTH) AF: 0.000188 AC: 11 AN: 58568

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152284 Hom.: 0 Cov.: 31 AF XY: 0.000121 AC XY: 9 AN XY: 74464

African (AFR) AF: 0.000144 AC: 6 AN: 41564

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000365 Hom.: 0

Bravo AF: 0.000155

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000214 AC: 26

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	0.12
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.082	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	0.63	N
PhyloP100		2.6
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.11
Sift	Benign	0.047	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.91	P
Vest4		0.18
MVP		0.61
MPC		0.16
ClinPred		0.072	T
GERP RS		3.8
Varity_R		0.046
gMVP		0.075
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs200385658; hg19: chr9-130191197;