16-30605001-T-C

Position:

• chr16-30605001-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138447.3(ZNF689):​c.766A>G​(p.Thr256Ala) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF689 NM_138447.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.39

Genes affected

ZNF689 (HGNC:25173): (zinc finger protein 689) Predicted to enable DNA-binding transcription factor 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 act upstream of or within skeletal muscle cell differentiation. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3283098).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF689	NM_138447.3	c.766A>G	p.Thr256Ala	missense_variant	3/3	ENST00000287461.8	NP_612456.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF689	ENST00000287461.8	c.766A>G	p.Thr256Ala	missense_variant	3/3	1	NM_138447.3	ENSP00000287461	P1
	ENST00000563540.1	n.189-3299T>C		intron_variant, non_coding_transcript_variant		3

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

Jul 19, 2023

The c.766A>G (p.T256A) alteration is located in exon 3 (coding exon 3) of the ZNF689 gene. This alteration results from a A to G substitution at nucleotide position 766, causing the threonine (T) at amino acid position 256 to be replaced by an alanine (A). 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	0.31
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	0.83	L
MutationTaster	Benign	0.55	D
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.10
Sift	Benign	0.042	D
Sift4G	Uncertain	0.046	D
Polyphen		0.98	D
Vest4		0.23
MutPred		0.28		Loss of phosphorylation at T256 (P = 0.0382);
MVP		0.35
MPC		1.8
ClinPred		0.99	D
GERP RS		2.8
Varity_R		0.23
gMVP		0.48

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: chr16-30616322;