15-42417837-C-G

Variant names:

• chr15-42417837-C-G
• NM_001366845.3:c.5632G>C

Variant summary

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

The NM_001366845.3(ZNF106):​c.5632G>C​(p.Ala1878Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF106 NM_001366845.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.16

Genes affected

ZNF106 (HGNC:12886): (zinc finger protein 106) Enables RNA binding activity. Predicted to be involved in insulin receptor signaling pathway. Predicted to be located in nuclear speck and nucleolus. Predicted to be active in cytosol and membrane. [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 rank	MANE	Protein	UniProt
ZNF106	NM_001366845.3	c.5632G>C	p.Ala1878Pro	missense_variant	Exon 21 of 22	ENST00000564754.7	NP_001353774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF106	ENST00000564754.7	c.5632G>C	p.Ala1878Pro	missense_variant	Exon 21 of 22	1	NM_001366845.3	ENSP00000456845.2

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

Jul 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.5563G>C (p.A1855P) alteration is located in exon 18 (coding exon 18) of the ZNF106 gene. This alteration results from a G to C substitution at nucleotide position 5563, causing the alanine (A) at amino acid position 1855 to be replaced by a proline (P). 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	0.98
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;.;T;.
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.43	T;T;T;T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	0.55	N;.;.;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.2	N;N;N;.
REVEL	Benign	0.25
Sift	Uncertain	0.0020	D;D;D;.
Sift4G	Benign	0.098	T;T;T;.
Polyphen		1.0	D;.;.;.
Vest4		0.59
MutPred		0.53		Loss of MoRF binding (P = 0.0527);.;.;.;
MVP		0.78
MPC		0.74
ClinPred		0.86	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.53
gMVP		0.51

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: chr15-42710035;