rs199941223

Variant names:

• chr12-110395217-G-T
• rs199941223
• NM_016238.3:c.292C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-110395217-G-T
• chr12-110395217-G-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016238.3(ANAPC7):​c.292C>A​(p.Leu98Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000119 in 1,604,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: ANAPC7 NM_016238.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.32
• Publications: 1 publications found

Genes affected

ANAPC7 (HGNC:17380): (anaphase promoting complex subunit 7) This gene encodes a tetratricopeptide repeat containing component of the anaphase promoting complex/cyclosome (APC/C), a large E3 ubiquitin ligase that controls cell cycle progression by targeting a number of cell cycle regulators such as B-type cyclins for 26S proteasome-mediated degradation through ubiquitination. The encoded protein is required for proper protein ubiquitination function of APC/C and for the interaction of APC/C with certain transcription coactivators. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2008]

ANAPC7 Gene-Disease associations (from GenCC):

• Ferguson-Bonni neurodevelopmental syndrome

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000258210 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.13897124).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016238.3. 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
	ANAPC7	NM_016238.3	MANE Select	c.292C>A	p.Leu98Ile	missense	Exon 3 of 11	NP_057322.3	Q9UJX3-1
	ANAPC7	NM_001385208.1		c.334C>A	p.Leu112Ile	missense	Exon 3 of 11	NP_001372137.1
	ANAPC7	NM_001137664.2		c.292C>A	p.Leu98Ile	missense	Exon 3 of 10	NP_001131136.2	Q9UJX3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANAPC7	ENST00000455511.9	TSL:1 MANE Select	c.292C>A	p.Leu98Ile	missense	Exon 3 of 11	ENSP00000394394.4	Q9UJX3-1
	ANAPC7	ENST00000450008.3	TSL:1	c.292C>A	p.Leu98Ile	missense	Exon 3 of 10	ENSP00000402314.3	Q9UJX3-2
	ANAPC7	ENST00000880053.1		c.292C>A	p.Leu98Ile	missense	Exon 3 of 12	ENSP00000550112.1

Frequencies

GnomAD3 genomes AF: 0.000132 AC: 20 AN: 152074 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

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: 0.000279

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000938 AC: 23 AN: 245116 AF XY: 0.0000979

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: 0.000197

Gnomad OTH exome AF: 0.000168

GnomAD4 exome AF: 0.000118 AC: 171 AN: 1452612 Hom.: 0 Cov.: 30 AF XY: 0.000119 AC XY: 86 AN XY: 722450

African (AFR) AF: 0.00 AC: 0 AN: 33056

American (AMR) AF: 0.00 AC: 0 AN: 42282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25770

East Asian (EAS) AF: 0.00 AC: 0 AN: 39572

South Asian (SAS) AF: 0.00 AC: 0 AN: 85270

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5246

European-Non Finnish (NFE) AF: 0.000150 AC: 166 AN: 1108296

Other (OTH) AF: 0.0000833 AC: 5 AN: 59992

GnomAD4 genome AF: 0.000132 AC: 20 AN: 152074 Hom.: 0 Cov.: 31 AF XY: 0.000108 AC XY: 8 AN XY: 74252

African (AFR) AF: 0.00 AC: 0 AN: 41402

American (AMR) AF: 0.0000656 AC: 1 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

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

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68024

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

Alfa AF: 0.000147 Hom.: 0

Bravo AF: 0.0000982

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000988 AC: 12

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	0.098
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.042	T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.030
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.3	L
PhyloP100		4.3
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.022
Sift	Benign	0.070	T
Sift4G	Benign	0.17	T
Polyphen		0.14	B
Vest4		0.43
MVP		0.67
MPC		0.76
ClinPred		0.098	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.12
Mutation Taster		=88/12	polymorphism

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: rs199941223; hg19: chr12-110833022;