15-42425015-C-T

Variant names:

• chr15-42425015-C-T
• rs201102338
• NM_001366845.3:c.5009G>A

Variant summary

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

The NM_001366845.3(ZNF106):​c.5009G>A​(p.Arg1670Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,508 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1670L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ZNF106 NM_001366845.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.66

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 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=0.04412949).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF106	NM_001366845.3	c.5009G>A	p.Arg1670Gln	missense_variant	Exon 16 of 22	ENST00000564754.7	NP_001353774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF106	ENST00000564754.7	c.5009G>A	p.Arg1670Gln	missense_variant	Exon 16 of 22	1	NM_001366845.3	ENSP00000456845.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250830 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135540

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461508 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726980

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.016	T;.;.;T;.
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.87	D;D;D;D;D
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.044	T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.2	N;.;.;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	1.0	N;N;N;N;.
REVEL	Benign	0.028
Sift	Benign	1.0	T;T;T;T;.
Sift4G	Benign	1.0	T;T;T;T;.
Polyphen		0.018	B;.;.;.;.
Vest4		0.084
MutPred		0.44		Gain of catalytic residue at R1647 (P = 0.0101);.;.;.;.;
MVP		0.15
MPC		0.17
ClinPred		0.17	T
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.018
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201102338; hg19: chr15-42717213;