16-30417568-C-G

Position:

• chr16-30417568-C-G

Variant summary

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

The NM_001142305.2(ZNF771):​c.155C>G​(p.Ala52Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000373 in 1,071,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: ZNF771 NM_001142305.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.367

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07035673).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF771	NM_001142305.2	c.155C>G	p.Ala52Gly	missense_variant	3/3	ENST00000319296.10	NP_001135777.1
ZNF771	NM_016643.4	c.155C>G	p.Ala52Gly	missense_variant	3/3		NP_057727.2
ZNF771	XM_047434196.1	c.230C>G	p.Ala77Gly	missense_variant	3/3		XP_047290152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF771	ENST00000319296.10	c.155C>G	p.Ala52Gly	missense_variant	3/3	1	NM_001142305.2	ENSP00000323945.5
ZNF771	ENST00000566625.2	c.141+9374C>G		intron_variant		1		ENSP00000460549.1
ZNF771	ENST00000434417.1	c.155C>G	p.Ala52Gly	missense_variant	3/3	2		ENSP00000416197.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000373 AC: 4 AN: 1071506 Hom.: 0 Cov.: 30 AF XY: 0.00000395 AC XY: 2 AN XY: 506698

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000400

Gnomad4 SAS exome AF: 0.0000501

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000468

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

Dec 17, 2023

The c.155C>G (p.A52G) 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 155, causing the alanine (A) at amino acid position 52 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	0.078
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.012	T;T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.098	.;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.070	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.55	N;N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.27	N;N
REVEL	Benign	0.024
Sift	Benign	0.25	T;T
Sift4G	Benign	0.51	T;T
Polyphen		0.41	B;B
Vest4		0.085
MutPred		0.15		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.37
MPC		1.7
ClinPred		0.19	T
GERP RS		2.6
Varity_R		0.058
gMVP		0.12

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

LitVar

Other links and lift over

dbSNP: rs1398444156; hg19: chr16-30428889;