19-52888193-C-T

Variant names:

• chr19-52888193-C-T
• rs558326325
• NM_001351774.2:c.76G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001351774.2(ZNF320):​c.76G>A​(p.Asp26Asn) 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. 15/22 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. D26H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF320 NM_001351774.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.762
• Publications: 1 publications found

Genes affected

ZNF320 (HGNC:13842): (zinc finger protein 320) ZNF320 encodes a Kruppel-like zinc finger protein. Members of this protein family are involved in activation or repression of transcription.[supplied by OMIM, Jul 2002]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13270211).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF320	NM_001351774.2	c.76G>A	p.Asp26Asn	missense_variant	Exon 5 of 6	ENST00000682928.1	NP_001338703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF320	ENST00000682928.1	c.76G>A	p.Asp26Asn	missense_variant	Exon 5 of 6		NM_001351774.2	ENSP00000506814.1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.18e-7 AC: 1 AN: 1392846 Hom.: 0 Cov.: 29 AF XY: 0.00000145 AC XY: 1 AN XY: 690434

African (AFR) AF: 0.00 AC: 0 AN: 30940

American (AMR) AF: 0.00 AC: 0 AN: 35546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22970

East Asian (EAS) AF: 0.00 AC: 0 AN: 39238

South Asian (SAS) AF: 0.00 AC: 0 AN: 78728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5424

European-Non Finnish (NFE) AF: 9.31e-7 AC: 1 AN: 1074034

Other (OTH) AF: 0.00 AC: 0 AN: 57494

GnomAD4 genome Cov.: 21

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.4
DANN	Benign	0.97
DEOGEN2	Benign	0.040	.;T;.;.;.;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0026	N
LIST_S2	Benign	0.061	T;.;T;T;T;T;.
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.13	T;T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.2	.;L;.;.;.;.;.
PhyloP100		-0.76
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.37	N;.;.;.;.;.;.
REVEL	Benign	0.036
Sift	Benign	0.22	T;.;.;.;.;.;.
Sift4G	Benign	0.23	T;T;.;.;T;.;.
Polyphen		0.042	.;B;.;.;.;.;.
Vest4		0.12
MutPred		0.58		Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP		0.055
MPC		1.9
ClinPred		0.046	T
GERP RS		-1.7
Varity_R		0.024
gMVP		0.034
Mutation Taster		=92/8	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: rs558326325; hg19: chr19-53391446;