Genetic Variant SAPCD2:p.Ala167Val (chr9-137069961-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178448.4(SAPCD2):c.500C>T(p.Ala167Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000823 in 1,252,142 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00051 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

SAPCD2
NM_178448.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.964

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16575357).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAPCD2	NM_178448.4 link	c.500C>T	p.Ala167Val	missense_variant	Exon 1 of 6	ENST00000409687.5	NP_848543.2	Q86UD0
SAPCD2	XM_011519180.4 link	c.500C>T	p.Ala167Val	missense_variant	Exon 1 of 7		XP_011517482.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAPCD2	ENST00000409687.5 link	c.500C>T	p.Ala167Val	missense_variant	Exon 1 of 6	1	NM_178448.4	ENSP00000386348.3		Q86UD0

Frequencies

GnomAD3 genomes

AF:

0.000514

AC:

AN:

151788

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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

GnomAD4 exome

AF:

0.0000227

AC:

AN:

1100248

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

526002

show subpopulations

Gnomad4 AFR exome

AF:

0.00101

Gnomad4 AMR exome

AF:

0.000119

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:

0.0000227

GnomAD4 genome

AF:

0.000514

AC:

AN:

151894

Hom.:

Cov.:

AF XY:

0.000498

AC XY:

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.00181

Gnomad4 AMR

AF:

0.000197

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

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000555

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 09, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.500C>T (p.A167V) alteration is located in exon 1 (coding exon 1) of the SAPCD2 gene. This alteration results from a C to T substitution at nucleotide position 500, causing the alanine (A) at amino acid position 167 to be replaced by a valine (V). 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

0.091

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.060

Eigen

Benign

0.11

Eigen_PC

Benign

-0.021

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.58

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.55

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.0

REVEL

Benign

0.082

Sift

Benign

0.13

Sift4G

Uncertain

0.049

Polyphen

1.0

Vest4

0.090

MutPred

0.17

Gain of relative solvent accessibility (P = 0.09);

MVP

0.54

MPC

0.33

ClinPred

0.71

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.9

Varity_R

0.088

gMVP

0.26

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over