9-137065604-G-C

Variant names:

• chr9-137065604-G-C
• rs749355882
• NM_178448.4:c.749C>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.749C>G​(p.Ala250Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. A250V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: SAPCD2 NM_178448.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.88
• 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=0.26066703).

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.749C>G	p.Ala250Gly	missense	Exon 3 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.749C>G	p.Ala250Gly	missense	Exon 3 of 6	ENSP00000386348.3	Q86UD0
	SAPCD2	ENST00000879034.1		c.839C>G	p.Ala280Gly	missense	Exon 4 of 7	ENSP00000549093.1
	SAPCD2	ENST00000940023.1		c.839C>G	p.Ala280Gly	missense	Exon 4 of 6	ENSP00000610082.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.042
Eigen_PC	Benign	0.037
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.9
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.23
Sift	Benign	0.077	T
Sift4G	Benign	0.080	T
Polyphen		0.80	P
Vest4		0.23
MutPred		0.23		Loss of helix (P = 0.0444)
MVP		0.72
MPC		0.92
ClinPred		0.84	D
GERP RS		2.4
Varity_R		0.070
gMVP		0.084
Mutation Taster		=90/10	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: rs749355882; hg19: chr9-139960056;