15-42428023-T-G

Variant names:

• chr15-42428023-T-G
• rs139485859
• NM_001366845.3:c.4993A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001366845.3(ZNF106):​c.4993A>C​(p.Ile1665Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. I1665V) has been classified as Uncertain significance.

• 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: 1.06
• Publications: 0 publications found

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]

ENSG00000310324 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045593172).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366845.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF106	NM_001366845.3	MANE Select	c.4993A>C	p.Ile1665Leu	missense	Exon 15 of 22	NP_001353774.1	H3BSS6
	ZNF106	NM_022473.3		c.4924A>C	p.Ile1642Leu	missense	Exon 12 of 19	NP_071918.1	Q9H2Y7-1
	ZNF106	NM_001381993.1		c.4792A>C	p.Ile1598Leu	missense	Exon 14 of 21	NP_001368922.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF106	ENST00000564754.7	TSL:1 MANE Select	c.4993A>C	p.Ile1665Leu	missense	Exon 15 of 22	ENSP00000456845.2	H3BSS6
	ZNF106	ENST00000263805.8	TSL:1	c.4924A>C	p.Ile1642Leu	missense	Exon 12 of 19	ENSP00000263805.4	Q9H2Y7-1
	ZNF106	ENST00000565380.5	TSL:1	c.2608A>C	p.Ile870Leu	missense	Exon 13 of 20	ENSP00000455674.1	Q9H2Y7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460810 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726818

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111104

Other (OTH) AF: 0.00 AC: 0 AN: 60348

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Benign	0.78
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.4	N
PhyloP100		1.1
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.020
Sift	Benign	0.40	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.24
MutPred		0.38		Loss of methylation at K1646 (P = 0.103)
MVP		0.15
MPC		0.15
ClinPred		0.086	T
GERP RS		-0.46
PromoterAI		-0.014	Neutral
Varity_R		0.027
gMVP		0.34

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

Other links and lift over

dbSNP: rs139485859; hg19: chr15-42720221;