rs151013418

Variant names:

• chr8-28351778-C-A
• rs151013418
• NM_018660.3:c.950G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-28351778-C-A
• chr8-28351778-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018660.3(ZNF395):​c.950G>T​(p.Arg317Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000146 in 1,577,620 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R317Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: ZNF395 NM_018660.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.99
• Publications: 0 publications found

Genes affected

ZNF395 (HGNC:18737): (zinc finger protein 395) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in cytosol and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

FBXO16 (HGNC:13618): (F-box protein 16) This gene encodes a member of the F-box protein family, members of which are characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into three classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbx class. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018660.3. 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
	ZNF395	NM_018660.3	MANE Select	c.950G>T	p.Arg317Leu	missense	Exon 7 of 10	NP_061130.1	Q9H8N7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF395	ENST00000344423.10	TSL:1 MANE Select	c.950G>T	p.Arg317Leu	missense	Exon 7 of 10	ENSP00000340494.5	Q9H8N7
	ZNF395	ENST00000523095.5	TSL:1	c.950G>T	p.Arg317Leu	missense	Exon 7 of 10	ENSP00000428452.1	Q9H8N7
	ZNF395	ENST00000523202.5	TSL:1	c.950G>T	p.Arg317Leu	missense	Exon 7 of 10	ENSP00000429640.1	Q9H8N7

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000136 AC: 3 AN: 220764 AF XY: 0.00000841

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000291

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000154 AC: 22 AN: 1425444 Hom.: 0 Cov.: 31 AF XY: 0.0000170 AC XY: 12 AN XY: 706306

African (AFR) AF: 0.00 AC: 0 AN: 33256

American (AMR) AF: 0.00 AC: 0 AN: 43746

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24342

East Asian (EAS) AF: 0.00 AC: 0 AN: 39478

South Asian (SAS) AF: 0.00 AC: 0 AN: 82176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39080

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5670

European-Non Finnish (NFE) AF: 0.0000200 AC: 22 AN: 1098370

Other (OTH) AF: 0.00 AC: 0 AN: 59326

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74332

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68016

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.65
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Uncertain	0.57	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.0
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.51
Sift	Benign	0.23	T
Sift4G	Benign	0.27	T
Polyphen		1.0	D
Vest4		0.67
MutPred		0.38		Loss of disorder (P = 0.0509)
MVP		0.66
MPC		1.1
ClinPred		0.96	D
GERP RS		5.0
PromoterAI		0.0037	Neutral
Varity_R		0.67
gMVP		0.49
Mutation Taster		=43/57	disease causing

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: rs151013418; hg19: chr8-28209295; COSMIC: COSV60429993; COSMIC: COSV60429993;