chr16-30525119-C-A

Position:

• chr16-30525119-C-A

Variant summary

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

The ENST00000380412.7(ZNF768):​c.1021G>T​(p.Gly341Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF768 ENST00000380412.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.76

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF768	NM_024671.4	c.1021G>T	p.Gly341Cys	missense_variant	2/2	ENST00000380412.7	NP_078947.3
ZNF768	XM_017023665.3	c.1093G>T	p.Gly365Cys	missense_variant	2/2		XP_016879154.1
ZNF768	XM_017023666.2	c.928G>T	p.Gly310Cys	missense_variant	2/2		XP_016879155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF768	ENST00000380412.7	c.1021G>T	p.Gly341Cys	missense_variant	2/2	1	NM_024671.4	ENSP00000369777	P2
ZNF768	ENST00000562803.1	c.928G>T	p.Gly310Cys	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

Oct 25, 2022

The c.1021G>T (p.G341C) alteration is located in exon 2 (coding exon 2) of the ZNF768 gene. This alteration results from a G to T substitution at nucleotide position 1021, causing the glycine (G) at amino acid position 341 to be replaced by a cysteine (C). 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	0.91
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.060	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Pathogenic	3.5	H;.
MutationTaster	Benign	0.99	D;D
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-8.8	D;.
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.66
MutPred		0.30		Loss of MoRF binding (P = 0.0901);.;
MVP		0.55
MPC		1.8
ClinPred		0.96	D
GERP RS		4.8
Varity_R		0.83
gMVP		0.63

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: chr16-30536440;