Genetic Variant NM_178448.4:c.500C>A (chr9-137069961-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178448.4(SAPCD2):c.500C>A(p.Ala167Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,100,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A167V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Consequence

SAPCD2
NM_178448.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.964

Publications

0 publications found

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]

SAPCD2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20796606).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178448.4. 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
	SAPCD2	NM_178448.4	MANE Select	c.500C>A	p.Ala167Glu	missense	Exon 1 of 6	NP_848543.2	Q86UD0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SAPCD2	ENST00000409687.5	TSL:1 MANE Select	c.500C>A	p.Ala167Glu	missense	Exon 1 of 6	ENSP00000386348.3	Q86UD0
SAPCD2	ENST00000879034.1		c.500C>A	p.Ala167Glu	missense	Exon 1 of 7	ENSP00000549093.1
SAPCD2	ENST00000940023.1		c.500C>A	p.Ala167Glu	missense	Exon 1 of 6	ENSP00000610082.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000182

AC:

AN:

1100248

Hom.:

Cov.:

AF XY:

0.00000380

AC XY:

AN XY:

526002

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22710

American (AMR)

AF:

0.000119

AC:

AN:

8396

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14326

East Asian (EAS)

AF:

0.00

AC:

AN:

26184

South Asian (SAS)

AF:

0.00

AC:

AN:

27522

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22252

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2920

European-Non Finnish (NFE)

AF:

0.00000107

AC:

AN:

931978

Other (OTH)

AF:

0.00

AC:

AN:

43960

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.090

Eigen

Benign

0.052

Eigen_PC

Benign

-0.072

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.49

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.55

PhyloP100

0.96

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.82

REVEL

Benign

0.11

Sift

Benign

0.53

Sift4G

Benign

0.23

Polyphen

1.0

Vest4

0.17

MutPred

0.17

Gain of solvent accessibility (P = 0.005)

MVP

0.44

MPC

0.42

ClinPred

0.56

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.9

Varity_R

0.19

gMVP

0.28

Mutation Taster

=84/16

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over