NM_178448.4:c.844G>C

Variant names:

• chr9-137065173-C-G
• rs966997511
• NM_178448.4:c.844G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_178448.4(SAPCD2):​c.844G>C​(p.Ala282Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000754 in 1,325,846 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. 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. A282T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: SAPCD2 NM_178448.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.45
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29246545).

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.844G>C	p.Ala282Pro	missense	Exon 4 of 6	NP_848543.2	Q86UD0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAPCD2	ENST00000409687.5	TSL:1 MANE Select	c.844G>C	p.Ala282Pro	missense	Exon 4 of 6	ENSP00000386348.3	Q86UD0
	SAPCD2	ENST00000879034.1		c.934G>C	p.Ala312Pro	missense	Exon 5 of 7	ENSP00000549093.1
	SAPCD2	ENST00000940023.1		c.934G>C	p.Ala312Pro	missense	Exon 5 of 6	ENSP00000610082.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.54e-7 AC: 1 AN: 1325846 Hom.: 0 Cov.: 31 AF XY: 0.00000154 AC XY: 1 AN XY: 648024

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29458

American (AMR) AF: 0.00 AC: 0 AN: 24888

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20452

East Asian (EAS) AF: 0.00 AC: 0 AN: 35702

South Asian (SAS) AF: 0.00 AC: 0 AN: 68624

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38062

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5338

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1048410

Other (OTH) AF: 0.0000182 AC: 1 AN: 54912

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.012
Eigen_PC	Benign	0.040
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.42	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.5
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.21
Sift	Benign	0.12	T
Sift4G	Uncertain	0.047	D
Polyphen		0.77	P
Vest4		0.27
MutPred		0.25		Loss of catalytic residue at A282 (P = 0.0281)
MVP		0.61
MPC		0.90
ClinPred		0.55	D
GERP RS		4.4
Varity_R		0.19
gMVP		0.13
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs966997511; hg19: chr9-139959625;