Variant 1-67430017-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001018069.2(SERBP1):c.284C>T(p.Thr95Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000869 in 1,611,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

SERBP1
NM_001018069.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.04

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09519309).

BS2

High AC in GnomAd at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SERBP1	NM_001018069.2 linkuse as main transcript	c.284C>T	p.Thr95Met	missense_variant	1/8	ENST00000361219.11
SERBP1	NM_001018067.2 linkuse as main transcript	c.284C>T	p.Thr95Met	missense_variant	1/8
SERBP1	NM_001018068.2 linkuse as main transcript	c.284C>T	p.Thr95Met	missense_variant	1/8
SERBP1	NM_015640.4 linkuse as main transcript	c.284C>T	p.Thr95Met	missense_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERBP1	ENST00000361219.11 linkuse as main transcript	c.284C>T	p.Thr95Met	missense_variant	1/8	1	NM_001018069.2		Q8NC51-3
SERBP1	ENST00000370995.6 linkuse as main transcript	c.284C>T	p.Thr95Met	missense_variant	1/8	1		P3	Q8NC51-1
SERBP1	ENST00000370990.5 linkuse as main transcript	c.284C>T	p.Thr95Met	missense_variant	1/8	1		A1	Q8NC51-2
SERBP1	ENST00000370994.8 linkuse as main transcript	c.284C>T	p.Thr95Met	missense_variant	1/8	1		A1	Q8NC51-4

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000203

AC:

AN:

245862

Hom.:

AF XY:

0.0000225

AC XY:

AN XY:

133568

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000591

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:

0.0000270

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1459248

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725912

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000906

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152296

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000102

ExAC

AF:

0.00000824

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

Oct 05, 2023

The c.284C>T (p.T95M) alteration is located in exon 1 (coding exon 1) of the SERBP1 gene. This alteration results from a C to T substitution at nucleotide position 284, causing the threonine (T) at amino acid position 95 to be replaced by a methionine (M). 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

0.089

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.40

Cadd

Uncertain

Dann

Uncertain

0.98

Eigen

Benign

0.14

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.69

LIST_S2

Uncertain

0.88

D;D;D;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.095

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L;L;L

MutationTaster

Benign

0.80

D;D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-2.4

N;N;N;N

REVEL

Benign

0.24

Sift

Benign

0.054

T;D;D;D

Sift4G

Benign

0.12

T;T;T;T

Polyphen

0.99, 0.99

.;D;D;.

Vest4

0.32

MVP

0.48

MPC

0.87

ClinPred

0.23

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.12

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