16-30571604-A-C

Position:

• chr16-30571604-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145271.4(ZNF688):​c.26T>G​(p.Leu9Arg) 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. 14/20 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: ZNF688 NM_145271.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.819

Genes affected

ZNF688 (HGNC:30489): (zinc finger protein 688) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.104019225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF688	NM_145271.4	c.26T>G	p.Leu9Arg	missense_variant	1/3	ENST00000223459.11
ZNF688	XM_047433653.1	c.26T>G	p.Leu9Arg	missense_variant	1/2
ZNF688	NM_001024683.2	c.155-481T>G		intron_variant
ZNF688	XM_047433654.1	c.155-481T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF688	ENST00000223459.11	c.26T>G	p.Leu9Arg	missense_variant	1/3	1	NM_145271.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Jun 18, 2021

The c.26T>G (p.L9R) alteration is located in exon 1 (coding exon 1) of the ZNF688 gene. This alteration results from a T to G substitution at nucleotide position 26, causing the leucine (L) at amino acid position 9 to be replaced by an arginine (R). 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	Benign	0.083
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	11
DANN	Benign	0.95
DEOGEN2	Benign	0.031	T;T;.
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.0019	N
LIST_S2	Benign	0.049	T;T;T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.2	L;.;.
MutationTaster	Benign	1.0	N;N;N;N
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.082
Sift	Benign	0.26	T;T;T
Sift4G	Uncertain	0.029	D;T;T
Polyphen		0.92	P;.;.
Vest4		0.22
MutPred		0.34		Gain of methylation at L9 (P = 0.0053);Gain of methylation at L9 (P = 0.0053);Gain of methylation at L9 (P = 0.0053);
MVP		0.092
MPC		0.52
ClinPred		0.46	T
GERP RS		0.36
Varity_R		0.29
gMVP		0.35

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: chr16-30582925;