NM_178448.4:c.829G>A

Variant names:

• chr9-137065524-C-T
• rs146866219
• NM_178448.4:c.829G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_178448.4(SAPCD2):​c.829G>A​(p.Ala277Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000192 in 1,597,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: SAPCD2 NM_178448.4 missense, splice_region
• Scores: Splicing: ADA: 0.00002569
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.789
• Publications: 3 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018688887).
• BP6: Variant 9-137065524-C-T is Benign according to our data. Variant chr9-137065524-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2591648.Status of the report is criteria_provided_single_submitter, 1 stars.

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.829G>A	p.Ala277Thr	missense splice_region	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.829G>A	p.Ala277Thr	missense splice_region	Exon 3 of 6	ENSP00000386348.3	Q86UD0
	SAPCD2	ENST00000879034.1		c.919G>A	p.Ala307Thr	missense splice_region	Exon 4 of 7	ENSP00000549093.1
	SAPCD2	ENST00000940023.1		c.919G>A	p.Ala307Thr	missense splice_region	Exon 4 of 6	ENSP00000610082.1

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152130 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000164 AC: 40 AN: 244186 AF XY: 0.000188

Gnomad AFR exome AF: 0.0000634

Gnomad AMR exome AF: 0.0000881

Gnomad ASJ exome AF: 0.000206

Gnomad EAS exome AF: 0.000332

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000237

Gnomad OTH exome AF: 0.000168

GnomAD4 exome AF: 0.000195 AC: 282 AN: 1445706 Hom.: 0 Cov.: 33 AF XY: 0.000177 AC XY: 127 AN XY: 716838

African (AFR) AF: 0.0000906 AC: 3 AN: 33130

American (AMR) AF: 0.0000681 AC: 3 AN: 44070

Ashkenazi Jewish (ASJ) AF: 0.0000775 AC: 2 AN: 25802

East Asian (EAS) AF: 0.000382 AC: 15 AN: 39240

South Asian (SAS) AF: 0.0000234 AC: 2 AN: 85588

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51194

Middle Eastern (MID) AF: 0.000458 AC: 2 AN: 4370

European-Non Finnish (NFE) AF: 0.000224 AC: 247 AN: 1102726

Other (OTH) AF: 0.000134 AC: 8 AN: 59586

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152130 Hom.: 0 Cov.: 34 AF XY: 0.000135 AC XY: 10 AN XY: 74312

African (AFR) AF: 0.0000724 AC: 3 AN: 41426

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10622

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

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000157 Hom.: 0

Bravo AF: 0.000230

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000190 AC: 23

EpiCase AF: 0.000164

EpiControl AF: 0.000417

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.068
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.030
DANN	Benign	0.92
DEOGEN2	Benign	0.028	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0061	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	-1.2	N
PhyloP100		-0.79
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.11
Sift	Benign	0.88	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.10
MVP		0.088
MPC		0.32
ClinPred		0.0088	T
GERP RS		-4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.026
gMVP		0.10
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000026
dbscSNV1_RF	Benign	0.0
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: rs146866219; hg19: chr9-139959976;