8-245252-A-T

Position:

• chr8-245252-A-T

Variant summary

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

The NM_001042416.3(ZNF596):​c.405A>T​(p.Arg135Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF596 NM_001042416.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.348

Genes affected

ZNF596 (HGNC:27268): (zinc finger protein 596) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF596 (HGNC:):

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=0.1653133).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF596	NM_001042416.3	c.405A>T	p.Arg135Ser	missense_variant	6/6	ENST00000398612.3	NP_001035881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF596	ENST00000398612.3	c.405A>T	p.Arg135Ser	missense_variant	6/6	5	NM_001042416.3	ENSP00000381613.1
ZNF596	ENST00000522866.5	c.*4A>T		downstream_gene_variant		3		ENSP00000477126.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Dec 16, 2023

The c.405A>T (p.R135S) alteration is located in exon 6 (coding exon 5) of the ZNF596 gene. This alteration results from a A to T substitution at nucleotide position 405, causing the arginine (R) at amino acid position 135 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	0.25
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	5.9
DANN	Benign	0.37
DEOGEN2	Benign	0.0030	.;T;T;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.00011	N
LIST_S2	Benign	0.44	T;.;.;T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.17	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.96	.;L;L;.;L
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.28	N;.;N;.;N
REVEL	Benign	0.048
Sift	Benign	0.082	T;.;T;.;T
Sift4G	Benign	0.35	T;T;T;.;T
Polyphen		0.0010	.;B;B;.;B
Vest4		0.10, 0.10, 0.10
MutPred		0.51		Loss of MoRF binding (P = 0.0145);Loss of MoRF binding (P = 0.0145);Loss of MoRF binding (P = 0.0145);Loss of MoRF binding (P = 0.0145);Loss of MoRF binding (P = 0.0145);
MVP		0.42
MPC		0.0019
ClinPred		0.050	T
GERP RS		1.3
Varity_R		0.089
gMVP		0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-195252;