11-75566929-C-G

Variant names:

• chr11-75566929-C-G
• NM_001235.5:c.580C>G

Variant summary

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

The NM_001235.5(SERPINH1):​c.580C>G​(p.Arg194Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,452,728 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.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SERPINH1 NM_001235.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.71

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]

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=0.25577646).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINH1	NM_001235.5	c.580C>G	p.Arg194Gly	missense_variant	Exon 2 of 5	ENST00000358171.8	NP_001226.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINH1	ENST00000358171.8	c.580C>G	p.Arg194Gly	missense_variant	Exon 2 of 5	1	NM_001235.5	ENSP00000350894.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1452728 Hom.: 0 Cov.: 70 AF XY: 0.00000138 AC XY: 1 AN XY: 723070

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T;T;.;T;T;T;.;T
Eigen	Benign	0.024
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.89	.;.;D;D;D;D;D;D
M_CAP	Uncertain	0.099	D
MetaRNN	Benign	0.26	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	1.2	L;L;.;.;.;L;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.57	N;N;N;N;N;N;N;N
REVEL	Uncertain	0.30
Sift	Benign	0.19	T;T;T;T;T;T;T;T
Sift4G	Benign	0.075	T;T;T;T;T;T;T;T
Polyphen		0.25	B;B;.;P;.;B;.;.
Vest4		0.20
MutPred		0.38		Loss of solvent accessibility (P = 0.0159);Loss of solvent accessibility (P = 0.0159);Loss of solvent accessibility (P = 0.0159);Loss of solvent accessibility (P = 0.0159);Loss of solvent accessibility (P = 0.0159);Loss of solvent accessibility (P = 0.0159);Loss of solvent accessibility (P = 0.0159);Loss of solvent accessibility (P = 0.0159);
MVP		0.90
MPC		0.30
ClinPred		0.55	D
GERP RS		3.7
Varity_R		0.22
gMVP		0.36

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-75277974;