16-30417981-C-G

Position:

• chr16-30417981-C-G

Variant summary

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

The ENST00000319296.10(ZNF771):​c.568C>G​(p.Leu190Val) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF771 ENST00000319296.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.737

Genes affected

ZNF771 (HGNC:29653): (zinc finger protein 771) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.3977605).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF771	NM_001142305.2	c.568C>G	p.Leu190Val	missense_variant	3/3	ENST00000319296.10	NP_001135777.1
ZNF771	NM_016643.4	c.568C>G	p.Leu190Val	missense_variant	3/3		NP_057727.2
ZNF771	XM_047434196.1	c.643C>G	p.Leu215Val	missense_variant	3/3		XP_047290152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF771	ENST00000319296.10	c.568C>G	p.Leu190Val	missense_variant	3/3	1	NM_001142305.2	ENSP00000323945	P1
ZNF771	ENST00000566625.2	c.141+9787C>G		intron_variant		1		ENSP00000460549
ZNF771	ENST00000434417.1	c.568C>G	p.Leu190Val	missense_variant	3/3	2		ENSP00000416197	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Nov 29, 2023

The c.568C>G (p.L190V) alteration is located in exon 3 (coding exon 2) of the ZNF771 gene. This alteration results from a C to G substitution at nucleotide position 568, causing the leucine (L) at amino acid position 190 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
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.78	.;T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.40	T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Pathogenic	0.95	D
PROVEAN	Uncertain	-2.8	D;D
REVEL	Uncertain	0.37
Sift	Uncertain	0.011	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.98	D;D
Vest4		0.18
MutPred		0.58		Loss of catalytic residue at L190 (P = 0.0266);Loss of catalytic residue at L190 (P = 0.0266);
MVP		0.77
MPC		2.8
ClinPred		0.97	D
GERP RS		1.6
Varity_R		0.25
gMVP		0.27

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: chr16-30429302;