7-57120162-A-C

Variant names:

• chr7-57120162-A-C
• rs1785848273
• NM_001370129.2:c.1253T>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001370129.2(ZNF479):​c.1253T>G​(p.Phe418Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,896 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF479 NM_001370129.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.13

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF479	NM_001370129.2	c.1253T>G	p.Phe418Cys	missense_variant	Exon 4 of 4	ENST00000319636.10	NP_001357058.1
ZNF479	NM_033273.3	c.1253T>G	p.Phe418Cys	missense_variant	Exon 5 of 5		NP_150376.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF479	ENST00000319636.10	c.1253T>G	p.Phe418Cys	missense_variant	Exon 4 of 4	1	NM_001370129.2	ENSP00000324518.6
ZNF479	ENST00000331162.8	c.1253T>G	p.Phe418Cys	missense_variant	Exon 5 of 5	1		ENSP00000333776.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460896 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726676

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1253T>G (p.F418C) alteration is located in exon 5 (coding exon 4) of the ZNF479 gene. This alteration results from a T to G substitution at nucleotide position 1253, causing the phenylalanine (F) at amino acid position 418 to be replaced by a cysteine (C). 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	Pathogenic	0.79
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.22	T;T;T
Eigen	Benign	-0.021
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.42	.;T;T
M_CAP	Benign	0.0013	T
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Benign	-0.84	T
MutationAssessor	Pathogenic	2.9	M;M;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-7.2	D;.;.
REVEL	Benign	0.14
Sift	Uncertain	0.012	D;.;.
Sift4G	Uncertain	0.013	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.18
MutPred		0.77		Loss of ubiquitination at K416 (P = 0.0613);Loss of ubiquitination at K416 (P = 0.0613);.;
MVP		0.77
MPC		2.3
ClinPred		0.91	D
GERP RS		0.89
Varity_R		0.070
gMVP		0.064

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

LitVar

Other links and lift over

dbSNP: rs1785848273; hg19: chr7-57187869;