chr9-137065173-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAPCD2	NM_178448.4	c.844G>C	p.Ala282Pro	missense_variant	Exon 4 of 6	ENST00000409687.5	NP_848543.2
SAPCD2	XM_011519180.4	c.934G>C	p.Ala312Pro	missense_variant	Exon 5 of 7		XP_011517482.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAPCD2	ENST00000409687.5	c.844G>C	p.Ala282Pro	missense_variant	Exon 4 of 6	1	NM_178448.4	ENSP00000386348.3

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

Gnomad4 AFR exome AF: 0.00

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: 0.0000182

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-139959625;