7-57120270-G-C

Variant names:

• chr7-57120270-G-C
• rs539820985
• NM_001370129.2:c.1145C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001370129.2(ZNF479):​c.1145C>G​(p.Thr382Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000023 in 1,611,190 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. T382I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: ZNF479 NM_001370129.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 0 publications found

Genes affected

ZNF479 (HGNC:23258): (zinc finger protein 479) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.029316574).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370129.2. 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
	ZNF479	NM_001370129.2	MANE Select	c.1145C>G	p.Thr382Arg	missense	Exon 4 of 4	NP_001357058.1	Q96JC4
	ZNF479	NM_033273.3		c.1145C>G	p.Thr382Arg	missense	Exon 5 of 5	NP_150376.1	Q96JC4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF479	ENST00000319636.10	TSL:1 MANE Select	c.1145C>G	p.Thr382Arg	missense	Exon 4 of 4	ENSP00000324518.6	Q96JC4
	ZNF479	ENST00000331162.8	TSL:1	c.1145C>G	p.Thr382Arg	missense	Exon 5 of 5	ENSP00000333776.4	Q96JC4

Frequencies

GnomAD3 genomes AF: 0.0000134 AC: 2 AN: 149624 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000403

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000483 AC: 12 AN: 248322 AF XY: 0.0000445

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000668

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000239 AC: 35 AN: 1461440 Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19 AN XY: 727004

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.000882 AC: 35 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111758

Other (OTH) AF: 0.00 AC: 0 AN: 60366

GnomAD4 genome AF: 0.0000134 AC: 2 AN: 149750 Hom.: 0 Cov.: 31 AF XY: 0.0000137 AC XY: 1 AN XY: 73048

African (AFR) AF: 0.00 AC: 0 AN: 40678

American (AMR) AF: 0.00 AC: 0 AN: 15030

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3448

East Asian (EAS) AF: 0.000404 AC: 2 AN: 4952

South Asian (SAS) AF: 0.00 AC: 0 AN: 4702

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 262

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67494

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000744 AC: 9

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.3
DANN	Benign	0.72
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0092	N
LIST_S2	Benign	0.024	T
M_CAP	Benign	0.00065	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.040	N
PhyloP100		-1.5
PrimateAI	Benign	0.38	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.016
Sift	Benign	0.057	T
Sift4G	Uncertain	0.043	D
Polyphen		0.30	B
Vest4		0.13
MutPred		0.37		Loss of phosphorylation at T382 (P = 0.0156)
MVP		0.12
MPC		1.0
ClinPred		0.050	T
GERP RS		-1.9
Varity_R		0.043
gMVP		0.016
Mutation Taster		=98/2	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: rs539820985; hg19: chr7-57187977;