ENST00000367723.8:c.31T>C

Variant names:

• chr1-172532503-T-C
• rs2239816
• ENST00000367723.8:c.31T>C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000367723.8(SUCO):​c.31T>C​(p.Ser11Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,612,794 control chromosomes in the GnomAD database, including 50,697 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.23 (4333 hom., cov: 32)
  • Exomes 𝑓: 0.25 (46364 hom.)
• Consequence: SUCO ENST00000367723.8 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.72

Genes affected

SUCO (HGNC:1240): (SUN domain containing ossification factor) Predicted to be involved in positive regulation of collagen biosynthetic process; positive regulation of osteoblast differentiation; and regulation of bone remodeling. Predicted to be located in rough endoplasmic reticulum. Predicted to be active in cytoplasm and membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0033645928).
• BP6: Variant 1-172532503-T-C is Benign according to our data. Variant chr1-172532503-T-C is described in ClinVar as [Benign]. Clinvar id is 3059072.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUCO	NM_016227.4	c.31T>C	p.Ser11Pro	missense_variant	Exon 1 of 23		NP_057311.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUCO	ENST00000367723.8	c.31T>C	p.Ser11Pro	missense_variant	Exon 1 of 23	1		ENSP00000356696.4

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35615 AN: 152044 Hom.: 4325 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.264

GnomAD3 exomes AF: 0.246 AC: 60309 AN: 244896 Hom.: 8012 AF XY: 0.255 AC XY: 33914 AN XY: 132976

Gnomad AFR exome AF: 0.199

Gnomad AMR exome AF: 0.200

Gnomad ASJ exome AF: 0.328

Gnomad EAS exome AF: 0.183

Gnomad SAS exome AF: 0.371

Gnomad FIN exome AF: 0.193

Gnomad NFE exome AF: 0.246

Gnomad OTH exome AF: 0.253

GnomAD4 exome AF: 0.248 AC: 361639 AN: 1460632 Hom.: 46364 Cov.: 34 AF XY: 0.252 AC XY: 183201 AN XY: 726520

Gnomad4 AFR exome AF: 0.204

Gnomad4 AMR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.325

Gnomad4 EAS exome AF: 0.196

Gnomad4 SAS exome AF: 0.372

Gnomad4 FIN exome AF: 0.191

Gnomad4 NFE exome AF: 0.243

Gnomad4 OTH exome AF: 0.257

GnomAD4 genome AF: 0.234 AC: 35637 AN: 152162 Hom.: 4333 Cov.: 32 AF XY: 0.234 AC XY: 17409 AN XY: 74404

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.268

Alfa AF: 0.247 Hom.: 8335

Bravo AF: 0.233

TwinsUK AF: 0.247 AC: 917

ALSPAC AF: 0.239 AC: 923

ESP6500AA AF: 0.205 AC: 787

ESP6500EA AF: 0.248 AC: 2051

ExAC AF: 0.251 AC: 30274

Asia WGS AF: 0.278 AC: 966 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SUCO-related disorder Benign:1

Oct 31, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.73
DANN	Benign	0.57
Eigen	Benign	-0.85
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.26	.;T
MetaRNN	Benign	0.0034	T;T
MetaSVM	Benign	-0.96	T
PROVEAN	Benign	-0.20	N;.
REVEL	Benign	0.0050
Sift	Pathogenic	0.0	D;.
Sift4G	Benign	0.35	T;T
Vest4		0.077
ClinPred		0.013	T
GERP RS		-1.3
gMVP		0.017

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2239816; hg19: chr1-172501643; COSMIC: COSV55263387; COSMIC: COSV55263387;