19-57253730-T-C

Position:

• chr19-57253730-T-C

Variant summary

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

The NM_001023563.4(ZNF805):​c.911T>C​(p.Leu304Ser) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF805 NM_001023563.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -4.05

Genes affected

ZNF805 (HGNC:23272): (zinc finger protein 805) 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 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=0.15074864).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF805	NM_001023563.4	c.911T>C	p.Leu304Ser	missense_variant	4/4	ENST00000414468.3	NP_001018857.2
ZNF805	NM_001145078.2	c.512T>C	p.Leu171Ser	missense_variant	3/3		NP_001138550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF805	ENST00000414468.3	c.911T>C	p.Leu304Ser	missense_variant	4/4	5	NM_001023563.4	ENSP00000412999	P1
ZNF805	ENST00000354309.4	c.512T>C	p.Leu171Ser	missense_variant	3/3	5		ENSP00000365414

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 97

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

Jan 31, 2024

The c.911T>C (p.L304S) alteration is located in exon 4 (coding exon 4) of the ZNF805 gene. This alteration results from a T to C substitution at nucleotide position 911, causing the leucine (L) at amino acid position 304 to be replaced by a serine (S). 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	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.00038	.;T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.51	T;T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	-0.26	.;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.11
Sift	Benign	0.12	T;T
Sift4G	Benign	0.55	T;T
Polyphen		1.0	.;D
Vest4		0.15
MutPred		0.32		.;Gain of disorder (P = 0.0106);
MVP		0.082
MPC		1.1
ClinPred		0.80	D
GERP RS		3.3
Varity_R		0.11
gMVP		0.040

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: chr19-57765098;