16-30524528-C-A

Variant names:

• chr16-30524528-C-A
• NM_024671.4:c.1612G>T

Variant summary

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

The NM_024671.4(ZNF768):​c.1612G>T​(p.Gly538Cys) variant causes a missense change. 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF768 NM_024671.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.25

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 rank	MANE	Protein	UniProt
ZNF768	NM_024671.4	c.1612G>T	p.Gly538Cys	missense_variant	Exon 2 of 2	ENST00000380412.7	NP_078947.3
ZNF768	XM_017023665.3	c.1684G>T	p.Gly562Cys	missense_variant	Exon 2 of 2		XP_016879154.1
ZNF768	XM_017023666.2	c.1519G>T	p.Gly507Cys	missense_variant	Exon 2 of 2		XP_016879155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF768	ENST00000380412.7	c.1612G>T	p.Gly538Cys	missense_variant	Exon 2 of 2	1	NM_024671.4	ENSP00000369777.5
ZNF768	ENST00000562803.1	c.1519G>T	p.Gly507Cys	missense_variant	Exon 2 of 2	3		ENSP00000456527.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1455522 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 724098

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1612G>T (p.G538C) 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 1612, causing the glycine (G) at amino acid position 538 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	Uncertain	0.34
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.63	T;T
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.18
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.013	D;D
Polyphen		1.0	D;.
Vest4		0.61
MutPred		0.33		Loss of methylation at R539 (P = 0.038);.;
MVP		0.51
MPC		1.8
ClinPred		0.96	D
GERP RS		5.3
Varity_R		0.31
gMVP		0.79

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: chr16-30535849; COSMIC: COSV63321826; COSMIC: COSV63321826;