7-57120141-G-C

Variant names:

• chr7-57120141-G-C
• rs1785846619
• NM_001370129.2:c.1274C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001370129.2(ZNF479):​c.1274C>G​(p.Thr425Ser) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZNF479 NM_001370129.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -4.95

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.093306184).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF479	NM_001370129.2	c.1274C>G	p.Thr425Ser	missense_variant	Exon 4 of 4	ENST00000319636.10	NP_001357058.1
ZNF479	NM_033273.3	c.1274C>G	p.Thr425Ser	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.1274C>G	p.Thr425Ser	missense_variant	Exon 4 of 4	1	NM_001370129.2	ENSP00000324518.6
ZNF479	ENST00000331162.8	c.1274C>G	p.Thr425Ser	missense_variant	Exon 5 of 5	1		ENSP00000333776.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1274C>G (p.T425S) alteration is located in exon 5 (coding exon 4) of the ZNF479 gene. This alteration results from a C to G substitution at nucleotide position 1274, causing the threonine (T) at amino acid position 425 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	0.19
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.6
DANN	Benign	0.67
DEOGEN2	Benign	0.036	T;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.029	.;T;T
M_CAP	Benign	0.00049	T
MetaRNN	Benign	0.093	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.34	N;N;.
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.4	D;.;.
REVEL	Benign	0.010
Sift	Benign	0.099	T;.;.
Sift4G	Benign	0.11	T;T;T
Polyphen		0.011	B;B;.
Vest4		0.029
MutPred		0.34		Gain of ubiquitination at K428 (P = 0.0762);Gain of ubiquitination at K428 (P = 0.0762);.;
MVP		0.17
MPC		0.79
ClinPred		0.041	T
GERP RS		0.89
Varity_R		0.020
gMVP		0.0092

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: rs1785846619; hg19: chr7-57187848;