20-25675129-C-A

Position:

• chr20-25675129-C-A

Variant summary

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

The NM_015655.4(ZNF337):​c.2159G>T​(p.Arg720Leu) 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. 13/21 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: ZNF337 NM_015655.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.275

Genes affected

ZNF337 (HGNC:15809): (zinc finger protein 337) This gene encodes a zinc finger domain containing protein. The function of this protein has yet to be determined. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ZNF337-AS1 (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=0.2166971).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF337	NM_015655.4	c.2159G>T	p.Arg720Leu	missense_variant	5/5	ENST00000252979.6	NP_056470.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF337	ENST00000252979.6	c.2159G>T	p.Arg720Leu	missense_variant	5/5	1	NM_015655.4	ENSP00000252979.5

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

Apr 05, 2023

The c.2159G>T (p.R720L) alteration is located in exon 5 (coding exon 4) of the ZNF337 gene. This alteration results from a G to T substitution at nucleotide position 2159, causing the arginine (R) at amino acid position 720 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	0.31
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.074	T;T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.77	.;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.1	D;D
REVEL	Benign	0.067
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.88	P;P
Vest4		0.31
MutPred		0.63		Loss of MoRF binding (P = 0.0284);Loss of MoRF binding (P = 0.0284);
MVP		0.31
MPC		0.25
ClinPred		0.95	D
GERP RS		-0.97
Varity_R		0.18
gMVP		0.035

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: chr20-25655765;