rs558566848

Variant names:

• chr9-114155970-G-A
• rs558566848
• NM_032888.4:c.20G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-114155970-G-A
• chr9-114155970-G-C
• chr9-114155970-G-T

Variant summary

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

The NM_032888.4(COL27A1):​c.20G>A​(p.Arg7Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000233 in 1,287,862 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R7L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 8.8e-7 (0 hom.)
• Consequence: COL27A1 NM_032888.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101
• Publications: 1 publications found

Genes affected

COL27A1 (HGNC:22986): (collagen type XXVII alpha 1 chain) This gene encodes a member of the fibrillar collagen family, and plays a role during the calcification of cartilage and the transition of cartilage to bone. The encoded protein product is a preproprotein. It includes an N-terminal signal peptide, which is followed by an N-terminal propetide, mature peptide and a C-terminal propeptide. The N-terminal propeptide contains thrombospondin N-terminal-like and laminin G-like domains. The mature peptide is a major triple-helical region. The C-terminal propeptide, also known as COLFI domain, plays crucial roles in tissue growth and repair. Mutations in this gene cause Steel syndrome. Alternatively spliced transcript variants have been found, but the full-length nature of some variants has not been determined. [provided by RefSeq, Sep 2014]

COL27A1 Gene-Disease associations (from GenCC):

• Steel syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)

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=0.2497629).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL27A1	NM_032888.4	c.20G>A	p.Arg7Gln	missense_variant	Exon 1 of 61	ENST00000356083.8	NP_116277.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL27A1	ENST00000356083.8	c.20G>A	p.Arg7Gln	missense_variant	Exon 1 of 61	1	NM_032888.4	ENSP00000348385.3

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151176 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 8.80e-7 AC: 1 AN: 1136686 Hom.: 0 Cov.: 31 AF XY: 0.00000184 AC XY: 1 AN XY: 544006

African (AFR) AF: 0.00 AC: 0 AN: 24506

American (AMR) AF: 0.00 AC: 0 AN: 16264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14934

East Asian (EAS) AF: 0.00 AC: 0 AN: 30202

South Asian (SAS) AF: 0.00 AC: 0 AN: 26014

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27814

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4406

European-Non Finnish (NFE) AF: 0.00000106 AC: 1 AN: 947040

Other (OTH) AF: 0.00 AC: 0 AN: 45506

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151176 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 73830

African (AFR) AF: 0.0000242 AC: 1 AN: 41284

American (AMR) AF: 0.00 AC: 0 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5104

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67674

Other (OTH) AF: 0.00 AC: 0 AN: 2070

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.53	T
M_CAP	Pathogenic	0.95	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.10
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.65	N
REVEL	Uncertain	0.29
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.12	T
Polyphen		0.56	P
Vest4		0.18
MutPred		0.20		Loss of MoRF binding (P = 6e-04);
MVP		0.15
MPC		0.13
ClinPred		0.61	D
GERP RS		-4.1
PromoterAI		0.033	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.16
gMVP		0.30
Mutation Taster		=92/8	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: rs558566848; hg19: chr9-116918250;