rs752118014

Variant names:

• chr9-137065148-C-A
• rs752118014
• NM_178448.4:c.869G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-137065148-C-A
• chr9-137065148-C-T

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.869G>T​(p.Arg290Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000732 in 1,365,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: 7.3e-7 (0 hom.)
• Consequence: SAPCD2 NM_178448.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.43
• 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=0.091216505).

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.869G>T	p.Arg290Leu	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.869G>T	p.Arg290Leu	missense	Exon 4 of 6	ENSP00000386348.3	Q86UD0
	SAPCD2	ENST00000879034.1		c.959G>T	p.Arg320Leu	missense	Exon 5 of 7	ENSP00000549093.1
	SAPCD2	ENST00000940023.1		c.959G>T	p.Arg320Leu	missense	Exon 5 of 6	ENSP00000610082.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.32e-7 AC: 1 AN: 1365602 Hom.: 0 Cov.: 31 AF XY: 0.00000149 AC XY: 1 AN XY: 671328

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30688

American (AMR) AF: 0.00 AC: 0 AN: 30586

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22534

East Asian (EAS) AF: 0.00 AC: 0 AN: 36464

South Asian (SAS) AF: 0.0000135 AC: 1 AN: 74340

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5490

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1065548

Other (OTH) AF: 0.00 AC: 0 AN: 56398

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.099
DANN	Benign	0.84
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.50	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.51	N
PhyloP100		-4.4
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.15
Sift	Benign	0.39	T
Sift4G	Benign	0.18	T
Polyphen		0.27	B
Vest4		0.29
MutPred		0.38		Loss of MoRF binding (P = 0.0053)
MVP		0.15
MPC		0.42
ClinPred		0.39	T
GERP RS		-5.5
Varity_R		0.048
gMVP		0.12
Mutation Taster		=100/0	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: rs752118014; hg19: chr9-139959600;