1-247100894-G-T

Position:

• chr1-247100894-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001142572.2(ZNF669):​c.617C>A​(p.Ser206Tyr) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF669 NM_001142572.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.473

Genes affected

ZNF669 (HGNC:25736): (zinc finger protein 669) 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061417013).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF669	NM_001142572.2	c.617C>A	p.Ser206Tyr	missense_variant	4/4	ENST00000448299.7	NP_001136044.1
ZNF669	NM_024804.3	c.875C>A	p.Ser292Tyr	missense_variant	4/4		NP_079080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF669	ENST00000448299.7	c.617C>A	p.Ser206Tyr	missense_variant	4/4	1	NM_001142572.2	ENSP00000404370	A2
ZNF669	ENST00000343381.10	c.875C>A	p.Ser292Tyr	missense_variant	4/4	1		ENSP00000342818	P2
ZNF669	ENST00000366501.1	c.*427C>A		3_prime_UTR_variant	4/4	3		ENSP00000355457

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Dec 15, 2023

The c.875C>A (p.S292Y) alteration is located in exon 4 (coding exon 4) of the ZNF669 gene. This alteration results from a C to A substitution at nucleotide position 875, causing the serine (S) at amino acid position 292 to be replaced by a tyrosine (Y). 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	Uncertain	0.46
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	5.7
DANN	Benign	0.70
DEOGEN2	Benign	0.020	.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.00044	N
LIST_S2	Benign	0.12	T;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.061	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.8	.;L
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Benign	0.038
Sift	Benign	0.42	T;T
Sift4G	Benign	0.33	T;T
Polyphen		0.012	.;B
Vest4		0.15
MutPred		0.53		.;Loss of disorder (P = 0.0143);
MVP		0.030
MPC		0.078
ClinPred		0.047	T
GERP RS		0.54
Varity_R		0.097
gMVP		0.031

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: chr1-247264196;