rs2239816

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-172532503-T-C
• chr1-172532503-T-G

Variant summary

Our verdict is Benign. The variant received -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. 12/15 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
• Publications: 21 publications found

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]

SUCO Gene-Disease associations (from GenCC):

• temporal lobe epilepsy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000300365 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000367723.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCO	NM_016227.4		c.31T>C	p.Ser11Pro	missense	Exon 1 of 23	NP_057311.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCO	ENST00000367723.8	TSL:1	c.31T>C	p.Ser11Pro	missense	Exon 1 of 23	ENSP00000356696.4
	ENSG00000300365	ENST00000771189.1		n.-89A>G		upstream_gene	N/A

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

GnomAD2 exomes AF: 0.246 AC: 60309 AN: 244896 AF XY: 0.255

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 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

African (AFR) AF: 0.204 AC: 6821 AN: 33462

American (AMR) AF: 0.200 AC: 8929 AN: 44586

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 8482 AN: 26084

East Asian (EAS) AF: 0.196 AC: 7796 AN: 39686

South Asian (SAS) AF: 0.372 AC: 32013 AN: 86064

European-Finnish (FIN) AF: 0.191 AC: 10183 AN: 53374

Middle Eastern (MID) AF: 0.333 AC: 1923 AN: 5768

European-Non Finnish (NFE) AF: 0.243 AC: 269969 AN: 1111268

Other (OTH) AF: 0.257 AC: 15523 AN: 60340

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

African (AFR) AF: 0.207 AC: 8576 AN: 41514

American (AMR) AF: 0.235 AC: 3594 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1186 AN: 3470

East Asian (EAS) AF: 0.187 AC: 969 AN: 5178

South Asian (SAS) AF: 0.370 AC: 1782 AN: 4820

European-Finnish (FIN) AF: 0.200 AC: 2114 AN: 10586

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16461 AN: 67986

Other (OTH) AF: 0.268 AC: 564 AN: 2108

Alfa AF: 0.244 Hom.: 10936

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

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SUCO-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
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
MetaSVM	Benign	-0.96	T
PhyloP100		-1.7
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.0050
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.35	T
Vest4		0.077
ClinPred		0.013	T
GERP RS		-1.3
PromoterAI		0.00060	Neutral
gMVP		0.017
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

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