16-30524929-C-T

Variant names:

• chr16-30524929-C-T
• NM_024671.4:c.1211G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024671.4(ZNF768):​c.1211G>A​(p.Gly404Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF768 NM_024671.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0430
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18678683).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024671.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF768	NM_024671.4	MANE Select	c.1211G>A	p.Gly404Asp	missense	Exon 2 of 2	NP_078947.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF768	ENST00000380412.7	TSL:1 MANE Select	c.1211G>A	p.Gly404Asp	missense	Exon 2 of 2	ENSP00000369777.5	Q9H5H4
	ZNF768	ENST00000562803.1	TSL:3	c.1118G>A	p.Gly373Asp	missense	Exon 2 of 2	ENSP00000456527.1	H3BS42

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461306 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726988

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111870

Other (OTH) AF: 0.00 AC: 0 AN: 60360

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.020
Eigen_PC	Benign	0.0049
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N
PhyloP100		0.043
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.15
Sift	Benign	0.40	T
Sift4G	Benign	0.58	T
Polyphen		1.0	D
Vest4		0.52
MutPred		0.26		Gain of ubiquitination at K408 (P = 0.0295)
MVP		0.58
MPC		2.0
ClinPred		0.76	D
GERP RS		4.7
Varity_R		0.15
gMVP		0.36

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

Other links and lift over

hg19: chr16-30536250; COSMIC: COSV63320889; COSMIC: COSV63320889;