1-172532503-T-G

Variant names:

• chr1-172532503-T-G
• rs2239816
• ENST00000367723.8:c.31T>G

Variant summary

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

The ENST00000367723.8(SUCO):​c.31T>G​(p.Ser11Ala) 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. 13/16 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. S11P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SUCO ENST00000367723.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 21 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):

• temporal lobe epilepsy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000300365 (HGNC:):

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=0.08803126).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCO	NM_016227.4		c.31T>G	p.Ser11Ala	missense	Exon 1 of 23	NP_057311.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCO	ENST00000367723.8	TSL:1	c.31T>G	p.Ser11Ala	missense	Exon 1 of 23	ENSP00000356696.4
	ENSG00000300365	ENST00000771189.1		n.-89A>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.65
DANN	Benign	0.67
Eigen	Benign	-0.85
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.96	T
PhyloP100		-1.7
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.0030
Sift	Pathogenic	0.0	D
Sift4G	Benign	1.0	T
Vest4		0.16
MutPred		0.22		Loss of loop (P = 0.0112)
MVP		0.085
ClinPred		0.47	T
GERP RS		-1.3
PromoterAI		0.031	Neutral
gMVP		0.0081
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs2239816; hg19: chr1-172501643;