rs139505436

Variant names:

• chr9-137066317-C-T
• rs139505436
• NM_178448.4:c.629G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_178448.4(SAPCD2):​c.629G>A​(p.Arg210His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,609,902 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00047 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000067 (0 hom.)
• Consequence: SAPCD2 NM_178448.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.610
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.031053096).

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.629G>A	p.Arg210His	missense	Exon 2 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.629G>A	p.Arg210His	missense	Exon 2 of 6	ENSP00000386348.3	Q86UD0
	SAPCD2	ENST00000879034.1		c.719G>A	p.Arg240His	missense	Exon 3 of 7	ENSP00000549093.1
	SAPCD2	ENST00000940023.1		c.719G>A	p.Arg240His	missense	Exon 3 of 6	ENSP00000610082.1

Frequencies

GnomAD3 genomes AF: 0.000466 AC: 71 AN: 152242 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000124 AC: 29 AN: 234566 AF XY: 0.0000933

Gnomad AFR exome AF: 0.00166

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000209

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000291

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000672 AC: 98 AN: 1457660 Hom.: 0 Cov.: 32 AF XY: 0.0000552 AC XY: 40 AN XY: 724884

African (AFR) AF: 0.00173 AC: 58 AN: 33440

American (AMR) AF: 0.0000225 AC: 1 AN: 44518

Ashkenazi Jewish (ASJ) AF: 0.000231 AC: 6 AN: 26004

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51730

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5426

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1111056

Other (OTH) AF: 0.000133 AC: 8 AN: 60128

GnomAD4 genome AF: 0.000466 AC: 71 AN: 152242 Hom.: 0 Cov.: 34 AF XY: 0.000511 AC XY: 38 AN XY: 74368

African (AFR) AF: 0.00164 AC: 68 AN: 41460

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000248 Hom.: 0

Bravo AF: 0.000586

ESP6500AA AF: 0.00183 AC: 8

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000158 AC: 19

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.12
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.61
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.15
Sift	Benign	0.041	D
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.26
MVP		0.46
MPC		0.48
ClinPred		0.092	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.25
Mutation Taster		=66/34	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: rs139505436; hg19: chr9-139960769; COSMIC: COSV68836423; COSMIC: COSV68836423;