rs978507323

Variant names:

• chr9-137069961-G-A
• rs978507323
• NM_178448.4:c.500C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-137069961-G-A
• chr9-137069961-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_178448.4(SAPCD2):​c.500C>T​(p.Ala167Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000823 in 1,252,142 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.00051 (1 hom., cov: 33)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: SAPCD2 NM_178448.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.964
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16575357).

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.500C>T	p.Ala167Val	missense	Exon 1 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.500C>T	p.Ala167Val	missense	Exon 1 of 6	ENSP00000386348.3	Q86UD0
	SAPCD2	ENST00000879034.1		c.500C>T	p.Ala167Val	missense	Exon 1 of 7	ENSP00000549093.1
	SAPCD2	ENST00000940023.1		c.500C>T	p.Ala167Val	missense	Exon 1 of 6	ENSP00000610082.1

Frequencies

GnomAD3 genomes AF: 0.000514 AC: 78 AN: 151788 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000227 AC: 25 AN: 1100248 Hom.: 0 Cov.: 29 AF XY: 0.0000152 AC XY: 8 AN XY: 526002

African (AFR) AF: 0.00101 AC: 23 AN: 22710

American (AMR) AF: 0.000119 AC: 1 AN: 8396

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14326

East Asian (EAS) AF: 0.00 AC: 0 AN: 26184

South Asian (SAS) AF: 0.00 AC: 0 AN: 27522

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2920

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 931978

Other (OTH) AF: 0.0000227 AC: 1 AN: 43960

GnomAD4 genome AF: 0.000514 AC: 78 AN: 151894 Hom.: 1 Cov.: 33 AF XY: 0.000498 AC XY: 37 AN XY: 74272

African (AFR) AF: 0.00181 AC: 75 AN: 41490

American (AMR) AF: 0.000197 AC: 3 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67884

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000427 Hom.: 0

Bravo AF: 0.000555

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	0.091
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.060	T
Eigen	Benign	0.11
Eigen_PC	Benign	-0.021
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.58	T
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.96
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.082
Sift	Benign	0.13	T
Sift4G	Uncertain	0.049	D
Polyphen		1.0	D
Vest4		0.090
MutPred		0.17		Gain of relative solvent accessibility (P = 0.09)
MVP		0.54
MPC		0.33
ClinPred		0.71	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.9
Varity_R		0.088
gMVP		0.26
Mutation Taster		=87/13	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: rs978507323; hg19: chr9-139964413;