19-55481224-G-T

Position:

• chr19-55481224-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000598519.2(ZNF628):​c.31G>T​(p.Asp11Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000708 in 1,411,836 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: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ZNF628 ENST00000598519.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.65

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2987669).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF628	NM_033113.3	c.31G>T	p.Asp11Tyr	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.31G>T	p.Asp11Tyr	missense_variant	3/3	1	NM_033113.3	ENSP00000469591.1
ZNF628	ENST00000591164.1	c.19G>T	p.Asp7Tyr	missense_variant	2/2	2		ENSP00000465905.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1411836 Hom.: 0 Cov.: 30 AF XY: 0.00000143 AC XY: 1 AN XY: 699140

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: 9.18e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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 20, 2023

The c.31G>T (p.A11S) alteration is located in exon 3 (coding exon 1) of the ZNF628 gene. This alteration results from a G to T substitution at nucleotide position 31, causing the alanine (A) at amino acid position 11 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	Pathogenic	0.63
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T;T;.
Eigen	Benign	0.097
Eigen_PC	Benign	0.018
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.64	T;T;T
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;.;.
MutationTaster	Benign	0.80	N
PrimateAI	Pathogenic	0.89	D
REVEL	Benign	0.12
Sift4G	Pathogenic	0.0010	D;T;D
Vest4		0.52
MVP		0.043
ClinPred		0.89	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1050850560; hg19: chr19-55992591;