19-55482512-C-T

Position:

• chr19-55482512-C-T

Variant summary

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

The NM_033113.3(ZNF628):​c.1319C>T​(p.Pro440Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000305 in 1,310,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: ZNF628 NM_033113.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.15

Genes affected

ZNF628 (HGNC:28054): (zinc finger protein 628) Zinc finger proteins (ZNFs), which bind nucleic acids, perform many key functions, the most important of which is regulating transcription. See ZNF91 (MIM 603971) for general information on ZNFs.[supplied by OMIM, Mar 2008]

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=0.11185232).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF628	NM_033113.3	c.1319C>T	p.Pro440Leu	missense_variant	3/3	ENST00000598519.2	NP_149104.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF628	ENST00000598519.2	c.1319C>T	p.Pro440Leu	missense_variant	3/3	1	NM_033113.3	ENSP00000469591.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000305 AC: 4 AN: 1310238 Hom.: 0 Cov.: 44 AF XY: 0.00000467 AC XY: 3 AN XY: 642044

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: 0.00000289

Gnomad4 OTH exome AF: 0.0000183

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2024

The c.1319C>T (p.P440L) alteration is located in exon 3 (coding exon 1) of the ZNF628 gene. This alteration results from a C to T substitution at nucleotide position 1319, causing the proline (P) at amino acid position 440 to be replaced by a leucine (L). 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	0.079
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.0054	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.69	N;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.1	.;N
REVEL	Benign	0.018
Sift	Benign	0.46	.;T
Sift4G	Uncertain	0.020	D;D
Vest4		0.35
MVP		0.043
ClinPred		0.16	T
GERP RS		1.6
Varity_R		0.037
gMVP		0.23

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: rs1341147671; hg19: chr19-55993879;