11-75566929-CGC-AGT

Variant names:

• chr11-75566929-CGC-AGT
• NM_001235.5:c.580_582delCGCinsAGT
• SERPINH1 p.Arg194Ser

Variant summary

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

The NM_001235.5(SERPINH1):​c.580_582delCGCinsAGT​(p.Arg194Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: SERPINH1 NM_001235.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.71
• Publications: 0 publications found

Genes affected

SERPINH1 (HGNC:1546): (serpin family H member 1) This gene encodes a member of the serpin superfamily of serine proteinase inhibitors. The encoded protein is localized to the endoplasmic reticulum and plays a role in collagen biosynthesis as a collagen-specific molecular chaperone. Autoantibodies to the encoded protein have been found in patients with rheumatoid arthritis. Expression of this gene may be a marker for cancer, and nucleotide polymorphisms in this gene may be associated with preterm birth caused by preterm premature rupture of membranes. Alternatively spliced transcript variants have been observed for this gene, and a pseudogene of this gene is located on the short arm of chromosome 9. [provided by RefSeq, May 2011]

SERPINH1 Gene-Disease associations (from GenCC):

• osteogenesis imperfecta type 10

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• osteogenesis imperfecta type 3

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001235.5. 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
	SERPINH1	NM_001235.5	MANE Select	c.580_582delCGCinsAGT	p.Arg194Ser	missense	N/A	NP_001226.2
	SERPINH1	NM_001207014.3		c.580_582delCGCinsAGT	p.Arg194Ser	missense	N/A	NP_001193943.1	P50454
	SERPINH1	NM_001440311.1		c.580_582delCGCinsAGT	p.Arg194Ser	missense	N/A	NP_001427240.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINH1	ENST00000358171.8	TSL:1 MANE Select	c.580_582delCGCinsAGT	p.Arg194Ser	missense	N/A	ENSP00000350894.4	P50454
	SERPINH1	ENST00000530284.5	TSL:1	c.580_582delCGCinsAGT	p.Arg194Ser	missense	N/A	ENSP00000436305.1	E9PPV6
	SERPINH1	ENST00000524558.5	TSL:2	c.580_582delCGCinsAGT	p.Arg194Ser	missense	N/A	ENSP00000434412.1	P50454

Frequencies

GnomAD3 genomes Cov.: 34

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.7

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-75277974;