19-52547579-C-G

Variant names:

• chr19-52547579-C-G
• rs1361640080
• NM_001039886.4:c.131C>G

Variant summary

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

The NM_001039886.4(ZNF808):​c.131C>G​(p.Ala44Gly) 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: 30)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF808 NM_001039886.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.342

Genes affected

ZNF808 (HGNC:33230): (zinc finger protein 808) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.097444415).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF808	NM_001039886.4	c.131C>G	p.Ala44Gly	missense_variant	Exon 4 of 5	ENST00000359798.9	NP_001034975.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF808	ENST00000359798.9	c.131C>G	p.Ala44Gly	missense_variant	Exon 4 of 5	5	NM_001039886.4	ENSP00000352846.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461830 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727218

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.131C>G (p.A44G) alteration is located in exon 4 (coding exon 2) of the ZNF808 gene. This alteration results from a C to G substitution at nucleotide position 131, causing the alanine (A) at amino acid position 44 to be replaced by a glycine (G). 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	0.16
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0059	T;.;.;.
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.0077	N
LIST_S2	Benign	0.020	T;T;T;T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.097	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.6	D;D;D;D
REVEL	Benign	0.018
Sift	Benign	0.066	T;D;T;D
Sift4G	Benign	0.11	T;T;D;T
Polyphen		0.0030	B;.;.;.
Vest4		0.20
MutPred		0.39		Loss of stability (P = 0.1318);Loss of stability (P = 0.1318);Loss of stability (P = 0.1318);Loss of stability (P = 0.1318);
MVP		0.19
MPC		0.12
ClinPred		0.055	T
GERP RS		2.4
Varity_R		0.14
gMVP		0.043

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1361640080; hg19: chr19-53050832;