Variant 3-150545769-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000239944.7(SERP1):c.94C>G(p.Pro32Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,454,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SERP1
ENST00000239944.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.71

Variant links:

Genes affected

SERP1 (HGNC:10759): (stress associated endoplasmic reticulum protein 1) Predicted to be involved in endoplasmic reticulum unfolded protein response and protein glycosylation. Predicted to act upstream of or within several processes, including multicellular organism aging; positive regulation of organ growth; and positive regulation of peptide hormone secretion. Located in cytoplasmic microtubule. [provided by Alliance of Genome Resources, Apr 2022]

SERP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.0926618).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERP1	NM_014445.4 linkuse as main transcript	c.94C>G	p.Pro32Ala	missense_variant	2/3	ENST00000239944.7	NP_055260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SERP1	ENST00000239944.7 linkuse as main transcript	c.94C>G	p.Pro32Ala	missense_variant	2/3	1	NM_014445.4	ENSP00000239944	P1
SERP1	ENST00000491660.1 linkuse as main transcript	c.94C>G	p.Pro32Ala	missense_variant	2/2	2		ENSP00000419472
SERP1	ENST00000479209.1 linkuse as main transcript	c.94C>G	p.Pro32Ala	missense_variant	3/4	2		ENSP00000420076	P1
SERP1	ENST00000487153.1 linkuse as main transcript	c.84+283C>G		intron_variant		4		ENSP00000420002

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000210

AC:

AN:

237880

Hom.:

AF XY:

0.0000312

AC XY:

AN XY:

128400

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000150

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000344

AC:

AN:

1454284

Hom.:

Cov.:

AF XY:

0.00000554

AC XY:

AN XY:

722656

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2024

The c.94C>G (p.P32A) alteration is located in exon 2 (coding exon 2) of the SERP1 gene. This alteration results from a C to G substitution at nucleotide position 94, causing the proline (P) at amino acid position 32 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.092

T;T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

0.038

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.68

T;.;T

M_CAP

Benign

0.0096

MetaRNN

Benign

0.093

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.28

N;N;N

REVEL

Benign

0.049

Sift

Benign

0.39

T;T;T

Sift4G

Benign

0.50

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.18

MutPred

0.25

Loss of glycosylation at P32 (P = 0.018);Loss of glycosylation at P32 (P = 0.018);Loss of glycosylation at P32 (P = 0.018);

MVP

0.18

MPC

0.90

ClinPred

0.84

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.71

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over