17-1766981-G-T

Variant names:

• chr17-1766981-G-T
• rs1039835757
• NM_002615.7:c.71G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_002615.7(SERPINF1):​c.71G>T​(p.Ser24Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,403,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SERPINF1 NM_002615.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM1: In a modified_residue Phosphoserine; by CK2 (size 0) in uniprot entity PEDF_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26791173).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINF1	NM_002615.7	c.71G>T	p.Ser24Ile	missense_variant	Exon 2 of 8	ENST00000254722.9	NP_002606.3
SERPINF1	NM_001329903.2	c.71G>T	p.Ser24Ile	missense_variant	Exon 2 of 8		NP_001316832.1
SERPINF1	NM_001329904.2	c.-477-2871G>T		intron_variant	Intron 1 of 6		NP_001316833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINF1	ENST00000254722.9	c.71G>T	p.Ser24Ile	missense_variant	Exon 2 of 8	1	NM_002615.7	ENSP00000254722.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000628 AC: 1 AN: 159262 Hom.: 0 AF XY: 0.0000119 AC XY: 1 AN XY: 84300

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 SAS exome AF: 0.0000435

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1403232 Hom.: 0 Cov.: 31 AF XY: 0.00000144 AC XY: 1 AN XY: 692534

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: 0.0000377

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.15	T;T;T;T;.
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.45	T;T;T;T;T
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.27	T;T;T;T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	1.8	L;.;.;.;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.9	N;.;.;.;.
REVEL	Benign	0.23
Sift	Uncertain	0.025	D;.;.;.;.
Sift4G	Benign	0.066	T;D;T;T;T
Polyphen		0.010	B;.;.;.;.
Vest4		0.27
MutPred		0.30		Loss of glycosylation at S24 (P = 0.0116);Loss of glycosylation at S24 (P = 0.0116);Loss of glycosylation at S24 (P = 0.0116);Loss of glycosylation at S24 (P = 0.0116);Loss of glycosylation at S24 (P = 0.0116);
MVP		0.93
MPC		0.094
ClinPred		0.11	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.11
gMVP		0.35

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

LitVar

Other links and lift over

dbSNP: rs1039835757; hg19: chr17-1670275;