11-75566427-C-A

Variant names:

• chr11-75566427-C-A
• rs763412073
• NM_001235.5:c.78C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001235.5(SERPINH1):​c.78C>A​(p.Ala26Ala) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A26A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SERPINH1 NM_001235.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.33
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• osteogenesis imperfecta type 3

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP7: Synonymous conserved (PhyloP=-3.33 with no splicing effect.

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.78C>A	p.Ala26Ala	synonymous	Exon 2 of 5	NP_001226.2
	SERPINH1	NM_001207014.3		c.78C>A	p.Ala26Ala	synonymous	Exon 3 of 6	NP_001193943.1	P50454
	SERPINH1	NM_001440311.1		c.78C>A	p.Ala26Ala	synonymous	Exon 3 of 6	NP_001427240.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINH1	ENST00000358171.8	TSL:1 MANE Select	c.78C>A	p.Ala26Ala	synonymous	Exon 2 of 5	ENSP00000350894.4	P50454
	SERPINH1	ENST00000530284.5	TSL:1	c.78C>A	p.Ala26Ala	synonymous	Exon 3 of 5	ENSP00000436305.1	E9PPV6
	SERPINH1	ENST00000524558.5	TSL:2	c.78C>A	p.Ala26Ala	synonymous	Exon 2 of 5	ENSP00000434412.1	P50454

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 241762 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: AC0 AF: 0.00 AC: 0 AN: 1459556 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726060

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86062

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51994

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111640

Other (OTH) AF: 0.00 AC: 0 AN: 60320

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.25
DANN	Benign	0.60
PhyloP100		-3.3

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: rs763412073; hg19: chr11-75277472;