9-137065662-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_178448.4(SAPCD2):​c.691C>G​(p.Gln231Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000936 in 1,602,586 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SAPCD2
NM_178448.4 missense

Scores

12
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.56
Variant links:
Genes affected
SAPCD2 (HGNC:28055): (suppressor APC domain containing 2) Involved in negative regulation of protein localization to cell cortex and positive regulation of cell population proliferation. Located in several cellular components, including apical cortex; apical junction complex; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SAPCD2NM_178448.4 linkc.691C>G p.Gln231Glu missense_variant Exon 3 of 6 ENST00000409687.5 NP_848543.2 Q86UD0
SAPCD2XM_011519180.4 linkc.781C>G p.Gln261Glu missense_variant Exon 4 of 7 XP_011517482.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SAPCD2ENST00000409687.5 linkc.691C>G p.Gln231Glu missense_variant Exon 3 of 6 1 NM_178448.4 ENSP00000386348.3 Q86UD0

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152230
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.000241
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
GnomAD3 exomes
AF:
0.00000811
AC:
2
AN:
246702
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
133512
show subpopulations
Gnomad AFR exome
AF:
0.000124
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS 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:
0.00000345
AC:
5
AN:
1450356
Hom.:
0
Cov.:
33
AF XY:
0.00000417
AC XY:
3
AN XY:
719674
show subpopulations
Gnomad4 AFR exome
AF:
0.000151
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152230
Hom.:
0
Cov.:
34
AF XY:
0.0000403
AC XY:
3
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000340
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000247
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 06, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.691C>G (p.Q231E) alteration is located in exon 3 (coding exon 3) of the SAPCD2 gene. This alteration results from a C to G substitution at nucleotide position 691, causing the glutamine (Q) at amino acid position 231 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.088
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.16
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.24
T
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.89
D
M_CAP
Uncertain
0.18
D
MetaRNN
Uncertain
0.47
T
MetaSVM
Uncertain
-0.011
T
MutationAssessor
Uncertain
2.0
M
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-1.8
N
REVEL
Uncertain
0.35
Sift
Benign
0.082
T
Sift4G
Uncertain
0.025
D
Polyphen
0.99
D
Vest4
0.49
MVP
0.77
MPC
0.60
ClinPred
0.30
T
GERP RS
4.1
Varity_R
0.20
gMVP
0.18

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs371106227; hg19: chr9-139960114; API