chr9-113042821-T-G

Position:

• chr9-113042821-T-G

Variant summary

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

The NM_003408.3(ZFP37):​c.1797A>C​(p.Lys599Asn) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZFP37 NM_003408.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.281

Genes affected

ZFP37 (HGNC:12863): (ZFP37 zinc finger protein) This gene encodes a transcription factor that belongs to a large family of zinc finger proteins. A similar protein in mouse is thought to play a role in regulating the structures of the nucleolus and centromere in neurons. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

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=0.24085033).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFP37	NM_003408.3	c.1797A>C	p.Lys599Asn	missense_variant	4/4	ENST00000374227.8
ZFP37	NM_001282515.2	c.1842A>C	p.Lys614Asn	missense_variant	4/4
ZFP37	NM_001282518.2	c.1800A>C	p.Lys600Asn	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFP37	ENST00000374227.8	c.1797A>C	p.Lys599Asn	missense_variant	4/4	1	NM_003408.3
ZFP37	ENST00000555206.5	c.1800A>C	p.Lys600Asn	missense_variant	4/4	1
ZFP37	ENST00000553380.1	c.1842A>C	p.Lys614Asn	missense_variant	4/4	2		P1

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 17, 2021

The c.1797A>C (p.K599N) alteration is located in exon 4 (coding exon 4) of the ZFP37 gene. This alteration results from a A to C substitution at nucleotide position 1797, causing the lysine (K) at amino acid position 599 to be replaced by an asparagine (N). 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	0.94
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;.;.
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.041
FATHMM_MKL	Benign	0.00039	N
LIST_S2	Benign	0.14	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.3	M;.;.
MutationTaster	Benign	0.79	D;D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-4.3	D;D;D
REVEL	Benign	0.12
Sift	Uncertain	0.0010	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.36
MutPred		0.56		Loss of methylation at K599 (P = 8e-04);.;.;
MVP		0.20
MPC		0.48
ClinPred		0.99	D
GERP RS		1.9
Varity_R		0.48
gMVP		0.034

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: chr9-115805101; COSMIC: COSV100953361;