chr19-52950517-T-G

Position:

• chr19-52950517-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001202457.3(ZNF816):​c.1258A>C​(p.Thr420Pro) 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 1,461,366 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZNF816 NM_001202457.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10

Genes affected

ZNF816 (HGNC:26995): (zinc finger protein 816) Predicted to enable DNA-binding transcription factor 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 integral component of membrane. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF816-ZNF321P (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2874599).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF816	NM_001202457.3	c.1258A>C	p.Thr420Pro	missense_variant	4/4	ENST00000444460.7
ZNF816-ZNF321P	NM_001202473.2	c.190+2234A>C		intron_variant
ZNF816	NM_001031665.4	c.1258A>C	p.Thr420Pro	missense_variant	5/5
ZNF816	NM_001202456.3	c.1258A>C	p.Thr420Pro	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF816	ENST00000444460.7	c.1258A>C	p.Thr420Pro	missense_variant	4/4	1	NM_001202457.3	P1
ZNF816	ENST00000357666.8	c.1258A>C	p.Thr420Pro	missense_variant	5/5	1		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461366 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727010

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: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	13
DANN	Benign	0.90
DEOGEN2	Benign	0.039	T;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.21	N
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	1.0	D;D;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-5.1	D;D
REVEL	Benign	0.11
Sift	Uncertain	0.027	D;D
Sift4G	Uncertain	0.043	D;D
Polyphen		1.0	D;D
Vest4		0.23
MutPred		0.39		Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP		0.16
MPC		0.49
ClinPred		0.78	D
GERP RS		1.8
Varity_R		0.46
gMVP		0.10

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-53453770;