9-137065556-C-T

Variant names:

• chr9-137065556-C-T
• rs138403381
• NM_178448.4:c.797G>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.797G>A​(p.Arg266His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000309 in 1,606,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00032 (0 hom.)
• Consequence: SAPCD2 NM_178448.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.44
• Publications: 1 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=0.032681793).

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.797G>A	p.Arg266His	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.797G>A	p.Arg266His	missense	Exon 3 of 6	ENSP00000386348.3	Q86UD0
	SAPCD2	ENST00000879034.1		c.887G>A	p.Arg296His	missense	Exon 4 of 7	ENSP00000549093.1
	SAPCD2	ENST00000940023.1		c.887G>A	p.Arg296His	missense	Exon 4 of 6	ENSP00000610082.1

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 36 AN: 152158 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000310 AC: 77 AN: 248028 AF XY: 0.000253

Gnomad AFR exome AF: 0.0000622

Gnomad AMR exome AF: 0.000407

Gnomad ASJ exome AF: 0.00343

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000233

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000317 AC: 461 AN: 1454808 Hom.: 0 Cov.: 33 AF XY: 0.000313 AC XY: 226 AN XY: 722746

African (AFR) AF: 0.0000600 AC: 2 AN: 33328

American (AMR) AF: 0.000359 AC: 16 AN: 44508

Ashkenazi Jewish (ASJ) AF: 0.00349 AC: 91 AN: 26038

East Asian (EAS) AF: 0.00 AC: 0 AN: 39440

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85918

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5192

European-Non Finnish (NFE) AF: 0.000294 AC: 326 AN: 1108264

Other (OTH) AF: 0.000400 AC: 24 AN: 60044

GnomAD4 genome AF: 0.000237 AC: 36 AN: 152158 Hom.: 0 Cov.: 34 AF XY: 0.000256 AC XY: 19 AN XY: 74332

African (AFR) AF: 0.00 AC: 0 AN: 41434

American (AMR) AF: 0.000131 AC: 2 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 67996

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.000249 Hom.: 0

Bravo AF: 0.000298

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000280 AC: 34

EpiCase AF: 0.000328

EpiControl AF: 0.000357

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	-0.12	T
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	18
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.41	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.74	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.033	T
MetaSVM	Uncertain	0.051	D
MutationAssessor	Benign	1.7	L
PhyloP100		1.4
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.51
Sift	Benign	0.14	T
Sift4G	Benign	0.085	T
Polyphen		0.97	D
Vest4		0.25
MVP		0.68
MPC		0.48
ClinPred		0.22	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.19
Mutation Taster		=93/7	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: rs138403381; hg19: chr9-139960008; COSMIC: COSV68836364; COSMIC: COSV68836364;