Variant 1-67430193-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001018069.2(SERBP1):c.108C>A(p.Asn36Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000807 in 1,610,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

SERBP1
NM_001018069.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.39

Variant links:

Genes affected

SERBP1 (HGNC:17860): (SERPINE1 mRNA binding protein 1) Enables SUMO binding activity; mRNA 3'-UTR binding activity; and ribosome binding activity. Involved in PML body organization. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SERBP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11470893).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SERBP1	NM_001018069.2 linkuse as main transcript	c.108C>A	p.Asn36Lys	missense_variant	1/8	ENST00000361219.11
SERBP1	NM_001018067.2 linkuse as main transcript	c.108C>A	p.Asn36Lys	missense_variant	1/8
SERBP1	NM_001018068.2 linkuse as main transcript	c.108C>A	p.Asn36Lys	missense_variant	1/8
SERBP1	NM_015640.4 linkuse as main transcript	c.108C>A	p.Asn36Lys	missense_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERBP1	ENST00000361219.11 linkuse as main transcript	c.108C>A	p.Asn36Lys	missense_variant	1/8	1	NM_001018069.2		Q8NC51-3
SERBP1	ENST00000370995.6 linkuse as main transcript	c.108C>A	p.Asn36Lys	missense_variant	1/8	1		P3	Q8NC51-1
SERBP1	ENST00000370990.5 linkuse as main transcript	c.108C>A	p.Asn36Lys	missense_variant	1/8	1		A1	Q8NC51-2
SERBP1	ENST00000370994.8 linkuse as main transcript	c.108C>A	p.Asn36Lys	missense_variant	1/8	1		A1	Q8NC51-4

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000617

AC:

AN:

1458466

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725590

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.00

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:

0.00000720

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000340

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

Dec 07, 2023

The c.108C>A (p.N36K) alteration is located in exon 1 (coding exon 1) of the SERBP1 gene. This alteration results from a C to A substitution at nucleotide position 108, causing the asparagine (N) at amino acid position 36 to be replaced by a lysine (K). 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

0.31

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.76

T;T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;L;L;L

MutationTaster

Benign

0.96

D;D;D;D

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.16

N;N;N;N

REVEL

Benign

0.060

Sift

Benign

0.40

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.24, 0.11

.;B;B;.

Vest4

0.23

MutPred

0.28

Gain of ubiquitination at N36 (P = 0.0258);Gain of ubiquitination at N36 (P = 0.0258);Gain of ubiquitination at N36 (P = 0.0258);Gain of ubiquitination at N36 (P = 0.0258);

MVP

0.44

MPC

1.0

ClinPred

0.34

GERP RS

4.0

Varity_R

0.22

gMVP

0.098

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