1-172533515-C-T

Variant names:

• chr1-172533515-C-T
• rs931206302
• NM_014283.5:c.62+18C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014283.5(SUCO):​c.62+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000726 in 1,378,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: SUCO NM_014283.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).

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.62+18C>T		intron	N/A	NP_055098.1	Q9UBS9-1
	SUCO	NM_016227.4		c.647+18C>T		intron	N/A	NP_057311.3	Q9UBS9-2
	SUCO	NM_001282750.2		c.62+18C>T		intron	N/A	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.62+18C>T		intron	N/A	ENSP00000263688.3	Q9UBS9-1
	SUCO	ENST00000367723.8	TSL:1	c.647+18C>T		intron	N/A	ENSP00000356696.4	Q9UBS9-2
	SUCO	ENST00000616058.4	TSL:1	c.-1468+18C>T		intron	N/A	ENSP00000479061.1	A0A087WV04

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000136 AC: 2 AN: 146922 AF XY: 0.0000129

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000134

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.26e-7 AC: 1 AN: 1378278 Hom.: 0 Cov.: 34 AF XY: 0.00000148 AC XY: 1 AN XY: 676116

African (AFR) AF: 0.00 AC: 0 AN: 31344

American (AMR) AF: 0.00 AC: 0 AN: 35028

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23386

East Asian (EAS) AF: 0.00 AC: 0 AN: 36188

South Asian (SAS) AF: 0.00 AC: 0 AN: 76096

European-Finnish (FIN) AF: 0.0000205 AC: 1 AN: 48850

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5590

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1064790

Other (OTH) AF: 0.00 AC: 0 AN: 57006

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.3
DANN	Benign	0.91
PhyloP100		-0.050
PromoterAI		0.0084	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs931206302; hg19: chr1-172502655;