chr9-137065166-C-G

Variant names:

• chr9-137065166-C-G
• NM_178448.4:c.851G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_178448.4(SAPCD2):​c.851G>C​(p.Ser284Thr) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SAPCD2 NM_178448.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.83
• 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 3 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity SAPC2_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32292527).

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.851G>C	p.Ser284Thr	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.851G>C	p.Ser284Thr	missense	Exon 4 of 6	ENSP00000386348.3	Q86UD0
	SAPCD2	ENST00000879034.1		c.941G>C	p.Ser314Thr	missense	Exon 5 of 7	ENSP00000549093.1
	SAPCD2	ENST00000940023.1		c.941G>C	p.Ser314Thr	missense	Exon 5 of 6	ENSP00000610082.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	0.11
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	18
DANN	Benign	0.70
DEOGEN2	Benign	0.077	T
Eigen	Benign	0.0013
Eigen_PC	Benign	-0.085
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.50	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.32	T
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Benign	1.3	L
PhyloP100		2.8
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.28
Sift	Benign	0.27	T
Sift4G	Benign	0.47	T
Polyphen		0.99	D
Vest4		0.31
MutPred		0.24		Gain of catalytic residue at S284 (P = 0.1145)
MVP		0.59
MPC		0.42
ClinPred		0.63	D
GERP RS		4.3
Varity_R		0.13
gMVP		0.14
Mutation Taster		=82/18	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

hg19: chr9-139959618;