19-34682804-T-G

Position:

• chr19-34682804-T-G

Variant summary

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

The NM_001289187.2(ZNF302):​c.37T>G​(p.Phe13Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF302 NM_001289187.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.54

Genes affected

ZNF302 (HGNC:13848): (zinc finger protein 302) This gene encodes a member of the zinc-finger protein family. The encoded protein contains seven C2H2-type zinc fingers and a KRAB domain, but its function has yet to be determined. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2014]

ZNF302 (HGNC:):

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	Protein	UniProt
ZNF302	NM_001289187.2	c.37T>G	p.Phe13Val	missense_variant	3/5	ENST00000505242.6	NP_001276116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF302	ENST00000505242.6	c.37T>G	p.Phe13Val	missense_variant	3/5	1	NM_001289187.2	ENSP00000421028.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461420 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726998

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Feb 10, 2022

The c.37T>G (p.F13V) alteration is located in exon 3 (coding exon 2) of the ZNF302 gene. This alteration results from a T to G substitution at nucleotide position 37, causing the phenylalanine (F) at amino acid position 13 to be replaced by a valine (V). 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
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T;T;.;T;.;T;.;.;T;.;.
Eigen	Uncertain	0.44
Eigen_PC	Benign	0.22
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.61	T;T;T;.;.;T;.;T;T;T;T
M_CAP	Benign	0.0013	T
MetaRNN	Uncertain	0.55	D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-5.6	.;.;D;D;D;D;D;D;D;D;D
REVEL	Benign	0.18
Sift	Uncertain	0.011	.;.;D;D;D;T;D;D;D;T;D
Sift4G	Uncertain	0.047	D;D;D;D;D;D;D;D;D;D;D
Polyphen		1.0, 0.99, 0.98	.;.;.;D;D;.;D;D;D;D;.
Vest4		0.71
MutPred		0.62		.;.;.;.;.;.;.;.;.;Loss of catalytic residue at F57 (P = 0.0094);.;
MVP		0.29
MPC		0.37
ClinPred		0.97	D
GERP RS		1.4
gMVP		0.25

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: chr19-35173709;