rs1907422119

Variant names:

• chr17-1766972-A-C
• rs1907422119
• NM_002615.7:c.62A>C

Variant summary

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

The NM_002615.7(SERPINF1):​c.62A>C​(p.Asn21Thr) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SERPINF1 NM_002615.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.96
• Publications: 0 publications found

Genes affected

SERPINF1 (HGNC:8824): (serpin family F member 1) This gene encodes a member of the serpin family that does not display the serine protease inhibitory activity shown by many of the other serpin proteins. The encoded protein is secreted and strongly inhibits angiogenesis. In addition, this protein is a neurotrophic factor involved in neuronal differentiation in retinoblastoma cells. Mutations in this gene were found in individuals with osteogenesis imperfecta, type VI. [provided by RefSeq, Aug 2016]

SERPINF1 Gene-Disease associations (from GenCC):

• osteogenesis imperfecta type 6

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• osteogenesis imperfecta type 3

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• osteogenesis imperfecta type 4

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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=0.11232743).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002615.7. 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
	SERPINF1	NM_002615.7	MANE Select	c.62A>C	p.Asn21Thr	missense	Exon 2 of 8	NP_002606.3
	SERPINF1	NM_001329903.2		c.62A>C	p.Asn21Thr	missense	Exon 2 of 8	NP_001316832.1	A0A140VKF3
	SERPINF1	NM_001329904.2		c.-477-2880A>C		intron	N/A	NP_001316833.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINF1	ENST00000254722.9	TSL:1 MANE Select	c.62A>C	p.Asn21Thr	missense	Exon 2 of 8	ENSP00000254722.4	P36955
	SERPINF1	ENST00000869424.1		c.62A>C	p.Asn21Thr	missense	Exon 2 of 8	ENSP00000539483.1
	SERPINF1	ENST00000869426.1		c.62A>C	p.Asn21Thr	missense	Exon 2 of 8	ENSP00000539485.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	0.0032	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	11
DANN	Benign	0.80
DEOGEN2	Benign	0.068	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.0
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.20
Sift	Benign	0.069	T
Sift4G	Benign	0.42	T
Polyphen		0.041	B
Vest4		0.44
MutPred		0.25		Gain of glycosylation at N21 (P = 0.0051)
MVP		0.79
MPC		0.077
ClinPred		0.089	T
GERP RS		2.3
Varity_R		0.10
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1907422119; hg19: chr17-1670266;