rs1555498115

Variant names:

• chr16-31061919-T-C
• rs1555498115
• NM_024706.5:c.1009A>G

Variant summary

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

The NM_024706.5(ZNF668):​c.1009A>G​(p.Lys337Glu) 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF668 NM_024706.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.928
• Publications: 0 publications found

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]

ZNF668 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with poor growth, large ears, and dysmorphic facies

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000232748 (HGNC:):

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=0.13071823).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024706.5. 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
	ZNF668	NM_024706.5	MANE Select	c.1009A>G	p.Lys337Glu	missense	Exon 3 of 3	NP_078982.3
	ZNF668	NM_001172669.2		c.1078A>G	p.Lys360Glu	missense	Exon 4 of 4	NP_001166140.1	Q96K58-2
	ZNF668	NM_001172668.2		c.1009A>G	p.Lys337Glu	missense	Exon 3 of 3	NP_001166139.1	Q96K58-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF668	ENST00000300849.5	TSL:1 MANE Select	c.1009A>G	p.Lys337Glu	missense	Exon 3 of 3	ENSP00000300849.4	Q96K58-1
	ZNF668	ENST00000426488.6	TSL:5	c.1078A>G	p.Lys360Glu	missense	Exon 4 of 4	ENSP00000403975.2	Q96K58-2
	ZNF668	ENST00000539836.3	TSL:5	c.1078A>G	p.Lys360Glu	missense	Exon 4 of 4	ENSP00000442573.3	Q96K58-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	23
DANN	Benign	0.96
Eigen	Benign	-0.032
Eigen_PC	Benign	0.0022
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.66	T
PhyloP100		0.93
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.16
Sift	Benign	0.47	T
Sift4G	Benign	0.47	T
Vest4		0.20
MutPred		0.42		Loss of methylation at K337 (P = 0)
MVP		0.50
MPC		1.2
ClinPred		0.45	T
GERP RS		4.5
gMVP		0.84

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

dbSNP: rs1555498115; hg19: chr16-31073240;