chr1-172533477-C-T

Variant names:

• chr1-172533477-C-T
• rs45505403
• NM_014283.5:c.42C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_014283.5(SUCO):​c.42C>T​(p.Leu14Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00294 in 1,564,858 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (12 hom.)
• Consequence: SUCO NM_014283.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.503
• Publications: 1 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 1-172533477-C-T is Benign according to our data. Variant chr1-172533477-C-T is described in ClinVar as Benign. ClinVar VariationId is 1637687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.503 with no splicing effect.
• BS2: High AC in GnomAd4 at 197 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014283.5. 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.42C>T	p.Leu14Leu	synonymous	Exon 1 of 24	NP_055098.1	Q9UBS9-1
	SUCO	NM_016227.4		c.627C>T	p.Leu209Leu	synonymous	Exon 2 of 23	NP_057311.3	Q9UBS9-2
	SUCO	NM_001282750.2		c.42C>T	p.Leu14Leu	synonymous	Exon 1 of 23	NP_001269679.1	B4DYM4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCO	ENST00000263688.4	TSL:1 MANE Select	c.42C>T	p.Leu14Leu	synonymous	Exon 1 of 24	ENSP00000263688.3	Q9UBS9-1
	SUCO	ENST00000367723.8	TSL:1	c.627C>T	p.Leu209Leu	synonymous	Exon 2 of 23	ENSP00000356696.4	Q9UBS9-2
	SUCO	ENST00000616058.4	TSL:1	c.-1488C>T		5_prime_UTR	Exon 1 of 22	ENSP00000479061.1	A0A087WV04

Frequencies

GnomAD3 genomes AF: 0.00129 AC: 196 AN: 152224 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000506

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00225

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00180 AC: 316 AN: 176038 AF XY: 0.00201

Gnomad AFR exome AF: 0.000199

Gnomad AMR exome AF: 0.000781

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000541

Gnomad NFE exome AF: 0.00302

Gnomad OTH exome AF: 0.00195

GnomAD4 exome AF: 0.00312 AC: 4405 AN: 1412516 Hom.: 12 Cov.: 34 AF XY: 0.00309 AC XY: 2154 AN XY: 698054

African (AFR) AF: 0.000279 AC: 9 AN: 32274

American (AMR) AF: 0.000713 AC: 27 AN: 37876

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25150

East Asian (EAS) AF: 0.00 AC: 0 AN: 37150

South Asian (SAS) AF: 0.00237 AC: 190 AN: 80126

European-Finnish (FIN) AF: 0.000441 AC: 22 AN: 49876

Middle Eastern (MID) AF: 0.00298 AC: 17 AN: 5702

European-Non Finnish (NFE) AF: 0.00372 AC: 4041 AN: 1085904

Other (OTH) AF: 0.00169 AC: 99 AN: 58458

GnomAD4 genome AF: 0.00129 AC: 197 AN: 152342 Hom.: 0 Cov.: 33 AF XY: 0.00119 AC XY: 89 AN XY: 74492

African (AFR) AF: 0.000505 AC: 21 AN: 41588

American (AMR) AF: 0.000392 AC: 6 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00225 AC: 153 AN: 68032

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.00231 Hom.: 0

Bravo AF: 0.00134

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	SUCO-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	9.2
DANN	Benign	0.89
PhyloP100		0.50
PromoterAI		0.065	Neutral
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs45505403; hg19: chr1-172502617;