9-113043113-G-A

Position:

• chr9-113043113-G-A

Variant summary

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

The NM_003408.3(ZFP37):​c.1505C>T​(p.Ser502Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,380 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZFP37 NM_003408.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.04

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFP37	NM_003408.3	c.1505C>T	p.Ser502Leu	missense_variant	4/4	ENST00000374227.8
ZFP37	NM_001282515.2	c.1550C>T	p.Ser517Leu	missense_variant	4/4
ZFP37	NM_001282518.2	c.1508C>T	p.Ser503Leu	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFP37	ENST00000374227.8	c.1505C>T	p.Ser502Leu	missense_variant	4/4	1	NM_003408.3
ZFP37	ENST00000555206.5	c.1508C>T	p.Ser503Leu	missense_variant	4/4	1
ZFP37	ENST00000553380.1	c.1550C>T	p.Ser517Leu	missense_variant	4/4	2		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461380 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726998

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

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 15, 2022

The c.1505C>T (p.S502L) alteration is located in exon 4 (coding exon 4) of the ZFP37 gene. This alteration results from a C to T substitution at nucleotide position 1505, causing the serine (S) at amino acid position 502 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	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.;.
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.00032	N
LIST_S2	Benign	0.63	T;T;T
M_CAP	Benign	0.0047	T
MetaRNN	Uncertain	0.49	T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.0	M;.;.
MutationTaster	Benign	0.95	N;N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-4.4	D;D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0010	D;D;D
Sift4G	Benign	0.071	T;T;T
Polyphen		0.99	D;.;P
Vest4		0.52
MutPred		0.68		Loss of disorder (P = 0.0231);.;.;
MVP		0.47
MPC		0.43
ClinPred		0.97	D
GERP RS		4.2
Varity_R		0.51
gMVP		0.067

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: chr9-115805393; COSMIC: COSV65288546;