9-137065149-G-C

Variant names:

• chr9-137065149-G-C
• rs757636026
• NM_178448.4:c.868C>G

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.868C>G​(p.Arg290Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000735 in 1,360,342 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. R290W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: SAPCD2 NM_178448.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91
• 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=0.20233357).

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.868C>G	p.Arg290Gly	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.868C>G	p.Arg290Gly	missense	Exon 4 of 6	ENSP00000386348.3	Q86UD0
	SAPCD2	ENST00000879034.1		c.958C>G	p.Arg320Gly	missense	Exon 5 of 7	ENSP00000549093.1
	SAPCD2	ENST00000940023.1		c.958C>G	p.Arg320Gly	missense	Exon 5 of 6	ENSP00000610082.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.35e-7 AC: 1 AN: 1360342 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 668244

African (AFR) AF: 0.00 AC: 0 AN: 30508

American (AMR) AF: 0.00 AC: 0 AN: 29800

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22272

East Asian (EAS) AF: 0.00 AC: 0 AN: 36426

South Asian (SAS) AF: 0.0000136 AC: 1 AN: 73704

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42756

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5450

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1063226

Other (OTH) AF: 0.00 AC: 0 AN: 56200

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.55	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.9
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.078
Sift	Benign	0.19	T
Sift4G	Benign	0.12	T
Polyphen		0.42	B
Vest4		0.35
MutPred		0.36		Loss of MoRF binding (P = 0.0076)
MVP		0.43
MPC		0.58
ClinPred		0.25	T
GERP RS		2.5
Varity_R		0.14
gMVP		0.099
Mutation Taster		=92/8	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: rs757636026; hg19: chr9-139959601;