Genetic Variant ENST00000367723.8:c.31T>C (chr1-172532503-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

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

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.72

Publications

21 publications found

Variant links:

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):

osteogenesis imperfecta
Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia
temporal lobe epilepsy
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

SUCO links:

ENSG00000300365 (HGNC:):

ENSG00000300365 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000367723.8, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

Sel.	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	Q9UBS9-2

Ensembl Transcripts

Sel.	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	Q9UBS9-2
	ENSG00000300365	ENST00000771189.1		n.-89A>G		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.234

AC:

35615

AN:

152044

Hom.:

4325

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.252

AC XY:

183201

AN XY:

726520

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

14154

28309

42463

56618

70772

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9256

18512

27768

37024

46280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.234

AC:

35637

AN:

152162

Hom.:

4333

Cov.:

AF XY:

0.234

AC XY:

17409

AN XY:

74404

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.242

AC:

16461

AN:

67986

Other (OTH)

AF:

0.268

AC:

564

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1428

2856

4284

5712

7140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

376

752

1128

1504

1880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.244

Hom.:

10936

Bravo

AF:

0.233

Asia WGS

AF:

0.278

AC:

966

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

SUCO-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.73

(source)

DANN

Benign

0.57

Eigen

Benign

-0.85

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.26

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.96

PhyloP100

-1.7

PROVEAN

Benign

-0.20

REVEL

Benign

0.0050

Sift

Pathogenic

0.0

Sift4G

Benign

0.35

PromoterAI

0.00060

Neutral

(source)

gMVP

0.017

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over