chr1-42851348-C-A

Position:

• chr1-42851348-C-A

Variant summary

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

The NM_001242739.2(ZNF691):​c.483C>A​(p.His161Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF691 NM_001242739.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.14

Genes affected

ZNF691 (HGNC:28028): (zinc finger protein 691) Predicted to enable DNA-binding transcription factor activity 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 located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF691	NM_001242739.2	c.483C>A	p.His161Gln	missense_variant	4/4	ENST00000651192.1	NP_001229668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF691	ENST00000651192.1	c.483C>A	p.His161Gln	missense_variant	4/4		NM_001242739.2	ENSP00000498913.1

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

Oct 25, 2024

The c.483C>A (p.H161Q) alteration is located in exon 4 (coding exon 2) of the ZNF691 gene. This alteration results from a C to A substitution at nucleotide position 483, causing the histidine (H) at amino acid position 161 to be replaced by a glutamine (Q). 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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.37	T;.;.;.;T;T;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.82	T;.;.;T;.;T;T
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.74	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.0028	D
MutationAssessor	Pathogenic	3.9	H;.;.;.;.;.;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	0.23	N;D;D;D;D;D;.
REVEL	Uncertain	0.47
Sift	Uncertain	0.0020	D;D;D;D;D;D;.
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D
Polyphen		1.0	D;.;.;.;.;.;.
Vest4		0.85
MutPred		0.65		Loss of methylation at R158 (P = 0.0445);.;.;.;.;Loss of methylation at R158 (P = 0.0445);.;
MVP		0.061
ClinPred		0.97	D
GERP RS		-7.5
Varity_R		0.84
gMVP		0.61

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: chr1-43317019;