chr9-137065173-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178448.4(SAPCD2):​c.844G>A​(p.Ala282Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000609 in 1,478,010 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000060 (0 hom.)
• Consequence: SAPCD2 NM_178448.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18646654).

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>A	p.Ala282Thr	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>A	p.Ala282Thr	missense	Exon 4 of 6	ENSP00000386348.3	Q86UD0
	SAPCD2	ENST00000879034.1		c.934G>A	p.Ala312Thr	missense	Exon 5 of 7	ENSP00000549093.1
	SAPCD2	ENST00000940023.1		c.934G>A	p.Ala312Thr	missense	Exon 5 of 6	ENSP00000610082.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152164 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000115 AC: 1 AN: 86790 AF XY: 0.00

Gnomad AFR exome AF: 0.000147

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000603 AC: 8 AN: 1325846 Hom.: 0 Cov.: 31 AF XY: 0.00000926 AC XY: 6 AN XY: 648024

African (AFR) AF: 0.0000339 AC: 1 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: 0.00000668 AC: 7 AN: 1048410

Other (OTH) AF: 0.00 AC: 0 AN: 54912

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152164 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74340

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.084	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.25	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	-0.55	N
PhyloP100		4.5
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.22
Sift	Benign	0.21	T
Sift4G	Uncertain	0.037	D
Polyphen		0.32	B
Vest4		0.16
MutPred		0.26		Gain of phosphorylation at A282 (P = 0.0341)
MVP		0.59
MPC		0.45
ClinPred		0.33	T
GERP RS		4.4
Varity_R		0.056
gMVP		0.086
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs966997511; hg19: chr9-139959625; COSMIC: COSV99081479; COSMIC: COSV99081479;