15-42428025-T-C

Variant names:

• chr15-42428025-T-C
• NM_001366845.3:c.4991A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001366845.3(ZNF106):​c.4991A>G​(p.Asn1664Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF106 NM_001366845.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.113

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12828141).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF106	NM_001366845.3	c.4991A>G	p.Asn1664Ser	missense_variant	Exon 15 of 22	ENST00000564754.7	NP_001353774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF106	ENST00000564754.7	c.4991A>G	p.Asn1664Ser	missense_variant	Exon 15 of 22	1	NM_001366845.3	ENSP00000456845.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461386 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 727024

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.00e-7

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	0.053
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.8
DANN	Benign	0.97
DEOGEN2	Benign	0.023	T;.;.;T;.
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.87	D;D;D;D;D
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.13	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.88	L;.;.;.;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.0	N;N;N;N;.
REVEL	Benign	0.056
Sift	Benign	0.56	T;T;T;T;.
Sift4G	Benign	0.52	T;T;T;T;.
Polyphen		0.0010	B;.;.;.;.
Vest4		0.28
MutPred		0.68		Gain of glycosylation at N1641 (P = 0.1015);.;.;.;.;
MVP		0.18
MPC		0.12
ClinPred		0.068	T
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.035
gMVP		0.26

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: chr15-42720223;