1-172532503-T-G

Position:

• chr1-172532503-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016227.4(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. 11/13 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 NM_016227.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08803126).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUCO	NM_016227.4	c.31T>G	p.Ser11Ala	missense_variant	1/23		NP_057311.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUCO	ENST00000367723.8	c.31T>G	p.Ser11Ala	missense_variant	1/23	1		ENSP00000356696.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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;T
MetaSVM	Benign	-0.96	T
PROVEAN	Benign	-0.090	N;.
REVEL	Benign	0.0030
Sift	Pathogenic	0.0	D;.
Sift4G	Benign	1.0	T;T
Vest4		0.16
MutPred		0.22		Loss of loop (P = 0.0112);Loss of loop (P = 0.0112);
MVP		0.085
ClinPred		0.47	T
GERP RS		-1.3
gMVP		0.0081

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2239816; hg19: chr1-172501643;