16-31061973-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_024706.5(ZNF668):c.955C>T(p.Gln319Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF668 NM_024706.5 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:3
• Conservation: PhyloP100: 4.04

Genes affected

ZNF668 (HGNC:25821): (zinc finger protein 668) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.487 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-31061973-G-A is Pathogenic according to our data. Variant chr16-31061973-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 1184621.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF668	NM_024706.5	c.955C>T	p.Gln319Ter	stop_gained	3/3	ENST00000300849.5
ZNF668	NM_001172669.2	c.1024C>T	p.Gln342Ter	stop_gained	4/4
ZNF668	NM_001172668.2	c.955C>T	p.Gln319Ter	stop_gained	3/3
ZNF668	NM_001172670.2	c.955C>T	p.Gln319Ter	stop_gained	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF668	ENST00000300849.5	c.955C>T	p.Gln319Ter	stop_gained	3/3	1	NM_024706.5	P1
	ENST00000622229.1	n.2550G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:3

Revision: no assertion criteria provided

Submissions by phenotype

Neurodevelopmental disorder with poor growth, large ears, and dysmorphic facies Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 10, 2023

- -

Severe short-limb dwarfism Pathogenic:1

Pathogenic, no assertion criteria provided

research

Department Of Translational Genomics (developmental Genetics Section), King Faisal Specialist Hospital & Research Centre

Apr 29, 2021

- -

Progressive microcephaly;C2315100:Failure to thrive;C3553450:Profound global developmental delay;na:marked facial dysmorphism Pathogenic:1

Pathogenic, no assertion criteria provided

research

Department Of Translational Genomics (developmental Genetics Section), King Faisal Specialist Hospital & Research Centre

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.65
Cadd	Pathogenic	40
Dann	Uncertain	1.0
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.97	D
MutationTaster	Benign	1.0	D;D;D;D;D;D
Vest4		0.23
ClinPred		1.0	D
GERP RS		4.8

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: chr16-31073294;