16-30571076-T-C

Position:

• chr16-30571076-T-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.244A>G​(p.Ser82Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,450,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S82R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZNF688 NM_145271.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.325

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=0.08937225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF688	NM_145271.4	c.244A>G	p.Ser82Gly	missense_variant	2/3	ENST00000223459.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF688	ENST00000223459.11	c.244A>G	p.Ser82Gly	missense_variant	2/3	1	NM_145271.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1450116 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 721468

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000246

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.062	T;.;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.013	T;T;T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.089	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.29	N;.;.
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.034
Sift	Uncertain	0.020	D;T;T
Sift4G	Uncertain	0.047	D;T;T
Polyphen		0.16	B;.;.
Vest4		0.24
MutPred		0.25		Loss of phosphorylation at S82 (P = 0.0373);.;Loss of phosphorylation at S82 (P = 0.0373);
MVP		0.17
MPC		0.38
ClinPred		0.29	T
GERP RS		4.1
Varity_R		0.26
gMVP		0.083

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1287324801; hg19: chr16-30582397;