1-172533200-T-C

Variant names:

• chr1-172533200-T-C
• rs2285143
• ENST00000367723.8:c.350T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_016227.4(SUCO):​c.350T>C​(p.Leu117Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 1,509,554 control chromosomes in the GnomAD database, including 58,598 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.34 (10044 hom., cov: 33)
  • Exomes 𝑓: 0.26 (48554 hom.)
• Consequence: SUCO NM_016227.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.02
• Publications: 14 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):

• osteogenesis imperfecta

  Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia
• temporal lobe epilepsy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.5810832E-5).
• BP6: Variant 1-172533200-T-C is Benign according to our data. Variant chr1-172533200-T-C is described in ClinVar as Benign. ClinVar VariationId is 3059036.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016227.4. 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
	SUCO	NM_014283.5	MANE Select	c.-236T>C		5_prime_UTR	Exon 1 of 24	NP_055098.1	Q9UBS9-1
	SUCO	NM_016227.4		c.350T>C	p.Leu117Pro	missense	Exon 2 of 23	NP_057311.3	Q9UBS9-2
	SUCO	NM_001282750.2		c.-236T>C		5_prime_UTR	Exon 1 of 23	NP_001269679.1	B4DYM4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCO	ENST00000367723.8	TSL:1	c.350T>C	p.Leu117Pro	missense	Exon 2 of 23	ENSP00000356696.4	Q9UBS9-2
	SUCO	ENST00000263688.4	TSL:1 MANE Select	c.-236T>C		5_prime_UTR	Exon 1 of 24	ENSP00000263688.3	Q9UBS9-1
	SUCO	ENST00000616058.4	TSL:1	c.-1765T>C		5_prime_UTR	Exon 1 of 22	ENSP00000479061.1	A0A087WV04

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50875 AN: 151810 Hom.: 10011 Cov.: 33

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.332

GnomAD2 exomes AF: 0.270 AC: 31088 AN: 115266 AF XY: 0.276

Gnomad AFR exome AF: 0.545

Gnomad AMR exome AF: 0.216

Gnomad ASJ exome AF: 0.318

Gnomad EAS exome AF: 0.176

Gnomad FIN exome AF: 0.185

Gnomad NFE exome AF: 0.240

Gnomad OTH exome AF: 0.278

GnomAD4 exome AF: 0.259 AC: 351257 AN: 1357634 Hom.: 48554 Cov.: 36 AF XY: 0.262 AC XY: 174655 AN XY: 666534

African (AFR) AF: 0.561 AC: 16817 AN: 29960

American (AMR) AF: 0.220 AC: 7018 AN: 31914

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 7489 AN: 23030

East Asian (EAS) AF: 0.197 AC: 6848 AN: 34820

South Asian (SAS) AF: 0.391 AC: 29473 AN: 75468

European-Finnish (FIN) AF: 0.187 AC: 7614 AN: 40804

Middle Eastern (MID) AF: 0.387 AC: 1528 AN: 3944

European-Non Finnish (NFE) AF: 0.244 AC: 258560 AN: 1061626

Other (OTH) AF: 0.284 AC: 15910 AN: 56068

GnomAD4 genome AF: 0.335 AC: 50951 AN: 151920 Hom.: 10044 Cov.: 33 AF XY: 0.332 AC XY: 24674 AN XY: 74276

African (AFR) AF: 0.554 AC: 22957 AN: 41468

American (AMR) AF: 0.273 AC: 4174 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1200 AN: 3470

East Asian (EAS) AF: 0.189 AC: 969 AN: 5132

South Asian (SAS) AF: 0.390 AC: 1879 AN: 4814

European-Finnish (FIN) AF: 0.200 AC: 2111 AN: 10580

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16558 AN: 67870

Other (OTH) AF: 0.336 AC: 706 AN: 2104

Alfa AF: 0.274 Hom.: 1233

Bravo AF: 0.348

TwinsUK AF: 0.248 AC: 919

ALSPAC AF: 0.241 AC: 928

ExAC AF: 0.256 AC: 5332

Asia WGS AF: 0.319 AC: 1111 AN: 3476

ClinVar

ClinVar submissions

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	0.18
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	12
DANN	Benign	0.56
Eigen	Benign	-0.89
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0096	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.000016	T
MetaSVM	Benign	-0.98	T
PhyloP100		-1.0
REVEL	Benign	0.012
Sift4G	Benign	0.17	T
Vest4		0.097
ClinPred		0.0060	T
GERP RS		-3.2
PromoterAI		0.041	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.4
gMVP		0.053
Mutation Taster		=296/4	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2285143; hg19: chr1-172502340; COSMIC: COSV55266876; COSMIC: COSV55266876;