16-30525179-G-T

Position:

• chr16-30525179-G-T

Variant summary

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

The NM_024671.4(ZNF768):​c.961C>A​(p.Arg321Ser) 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: ZNF768 NM_024671.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.148

Genes affected

ZNF768 (HGNC:26273): (zinc finger protein 768) Enables RNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located 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=0.16913664).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF768	NM_024671.4	c.961C>A	p.Arg321Ser	missense_variant	2/2	ENST00000380412.7	NP_078947.3
ZNF768	XM_017023665.3	c.1033C>A	p.Arg345Ser	missense_variant	2/2		XP_016879154.1
ZNF768	XM_017023666.2	c.868C>A	p.Arg290Ser	missense_variant	2/2		XP_016879155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF768	ENST00000380412.7	c.961C>A	p.Arg321Ser	missense_variant	2/2	1	NM_024671.4	ENSP00000369777	P2
ZNF768	ENST00000562803.1	c.868C>A	p.Arg290Ser	missense_variant	2/2	3		ENSP00000456527	A2

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

Dec 15, 2023

The c.961C>A (p.R321S) alteration is located in exon 2 (coding exon 2) of the ZNF768 gene. This alteration results from a C to A substitution at nucleotide position 961, causing the arginine (R) at amino acid position 321 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	Uncertain	0.40
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0070	T;.
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.36	N
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.33	N;.
MutationTaster	Benign	0.55	D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.74	N;.
REVEL	Benign	0.27
Sift	Uncertain	0.019	D;.
Sift4G	Uncertain	0.021	D;D
Polyphen		0.96	D;.
Vest4		0.28
MutPred		0.40		Gain of ubiquitination at K324 (P = 0.0312);.;
MVP		0.72
MPC		1.7
ClinPred		0.65	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.81

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: chr16-30536500;