1-172533200-T-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016227.4(SUCO):​c.350T>A​(p.Leu117Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L117P) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SUCO NM_016227.4 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08930907).

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>A		5_prime_UTR	Exon 1 of 24	NP_055098.1	Q9UBS9-1
	SUCO	NM_016227.4		c.350T>A	p.Leu117Gln	missense	Exon 2 of 23	NP_057311.3	Q9UBS9-2
	SUCO	NM_001282750.2		c.-236T>A		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>A	p.Leu117Gln	missense	Exon 2 of 23	ENSP00000356696.4	Q9UBS9-2
	SUCO	ENST00000263688.4	TSL:1 MANE Select	c.-236T>A		5_prime_UTR	Exon 1 of 24	ENSP00000263688.3	Q9UBS9-1
	SUCO	ENST00000616058.4	TSL:1	c.-1765T>A		5_prime_UTR	Exon 1 of 22	ENSP00000479061.1	A0A087WV04

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000868 AC: 1 AN: 115266 AF XY: 0.00

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: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.36e-7 AC: 1 AN: 1358100 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 666792

African (AFR) AF: 0.00 AC: 0 AN: 29986

American (AMR) AF: 0.00 AC: 0 AN: 31998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23054

East Asian (EAS) AF: 0.00 AC: 0 AN: 34836

South Asian (SAS) AF: 0.0000132 AC: 1 AN: 75520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40842

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3946

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1061830

Other (OTH) AF: 0.00 AC: 0 AN: 56088

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1233

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.93
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.32	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-0.95	T
PhyloP100		-1.0
REVEL	Benign	0.010
Sift4G	Benign	0.19	T
Vest4		0.19
MVP		0.088
ClinPred		0.33	T
GERP RS		-3.2
PromoterAI		0.035	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.4
gMVP		0.037
Mutation Taster		=296/4	polymorphism

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;