rs201102338

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr15-42425015-C-A
• chr15-42425015-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001366845.3(ZNF106):​c.5009G>T​(p.Arg1670Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,613,656 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000045 (0 hom.)
• Consequence: ZNF106 NM_001366845.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.66
• Publications: 5 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.059304357).

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.5009G>T	p.Arg1670Leu	missense	Exon 16 of 22	NP_001353774.1	H3BSS6
	ZNF106	NM_022473.3		c.4940G>T	p.Arg1647Leu	missense	Exon 13 of 19	NP_071918.1	Q9H2Y7-1
	ZNF106	NM_001381993.1		c.4808G>T	p.Arg1603Leu	missense	Exon 15 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.5009G>T	p.Arg1670Leu	missense	Exon 16 of 22	ENSP00000456845.2	H3BSS6
	ZNF106	ENST00000263805.8	TSL:1	c.4940G>T	p.Arg1647Leu	missense	Exon 13 of 19	ENSP00000263805.4	Q9H2Y7-1
	ZNF106	ENST00000565380.5	TSL:1	c.2624G>T	p.Arg875Leu	missense	Exon 14 of 20	ENSP00000455674.1	Q9H2Y7-2

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000917

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000837 AC: 21 AN: 250830 AF XY: 0.000103

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000970

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.0000452 AC: 66 AN: 1461502 Hom.: 0 Cov.: 31 AF XY: 0.0000426 AC XY: 31 AN XY: 726974

African (AFR) AF: 0.000179 AC: 6 AN: 33476

American (AMR) AF: 0.000157 AC: 7 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5756

European-Non Finnish (NFE) AF: 0.0000378 AC: 42 AN: 1111780

Other (OTH) AF: 0.0000497 AC: 3 AN: 60388

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152154 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74328

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.000917 AC: 14 AN: 15272

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: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000947 Hom.: 0

Bravo AF: 0.0000642

ExAC AF: 0.000115 AC: 14

EpiCase AF: 0.000164

EpiControl AF: 0.000178

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	Benign	0.15
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Benign	0.87
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.55	N
PhyloP100		2.7
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.38	N
REVEL	Benign	0.090
Sift	Benign	0.088	T
Sift4G	Uncertain	0.038	D
Polyphen		0.59	P
Vest4		0.51
MVP		0.26
MPC		0.23
ClinPred		0.065	T
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.053
gMVP		0.37
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs201102338; hg19: chr15-42717213;