chr15-42417866-G-A

Variant names:

• chr15-42417866-G-A
• rs767057566
• NM_001366845.3:c.5603C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001366845.3(ZNF106):​c.5603C>T​(p.Thr1868Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,613,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: ZNF106 NM_001366845.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.52
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3121788).

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.5603C>T	p.Thr1868Ile	missense	Exon 21 of 22	NP_001353774.1	H3BSS6
	ZNF106	NM_022473.3		c.5534C>T	p.Thr1845Ile	missense	Exon 18 of 19	NP_071918.1	Q9H2Y7-1
	ZNF106	NM_001381993.1		c.5402C>T	p.Thr1801Ile	missense	Exon 20 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.5603C>T	p.Thr1868Ile	missense	Exon 21 of 22	ENSP00000456845.2	H3BSS6
	ZNF106	ENST00000263805.8	TSL:1	c.5534C>T	p.Thr1845Ile	missense	Exon 18 of 19	ENSP00000263805.4	Q9H2Y7-1
	ZNF106	ENST00000565380.5	TSL:1	c.3218C>T	p.Thr1073Ile	missense	Exon 19 of 20	ENSP00000455674.1	Q9H2Y7-2

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152218 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000557 AC: 14 AN: 251288 AF XY: 0.0000736

Gnomad AFR exome AF: 0.000862

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461730 Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 11 AN XY: 727182

African (AFR) AF: 0.000478 AC: 16 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111942

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152218 Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7 AN XY: 74356

African (AFR) AF: 0.000338 AC: 14 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68050

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000986 Hom.: 0

Bravo AF: 0.000147

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	-0.0053	T
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.9	L
PhyloP100		7.5
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.29
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.75
MutPred		0.38		Loss of disorder (P = 0.0662)
MVP		0.81
MPC		0.67
ClinPred		0.29	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.35
gMVP		0.67
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs767057566; hg19: chr15-42710064;