1-67420119-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_001018069.2(SERBP1):c.841A>C(p.Ile281Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SERBP1 NM_001018069.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.02

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a cross_link Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate (size 0) in uniprot entity PAIRB_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16249937).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERBP1	NM_001018069.2	c.841A>C	p.Ile281Leu	missense_variant	6/8	ENST00000361219.11
SERBP1	NM_001018067.2	c.886A>C	p.Ile296Leu	missense_variant	6/8
SERBP1	NM_001018068.2	c.868A>C	p.Ile290Leu	missense_variant	6/8
SERBP1	NM_015640.4	c.823A>C	p.Ile275Leu	missense_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERBP1	ENST00000361219.11	c.841A>C	p.Ile281Leu	missense_variant	6/8	1	NM_001018069.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461470 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727062

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

The c.886A>C (p.I296L) alteration is located in exon 6 (coding exon 6) of the SERBP1 gene. This alteration results from a A to C substitution at nucleotide position 886, causing the isoleucine (I) at amino acid position 296 to be replaced by a leucine (L). 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	0.14
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
Cadd	Benign	22
Dann	Benign	0.86
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D;T;T;D
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.99	D;D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	0.85	N;N;N;N
REVEL	Benign	0.11
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.023, 0.0040	.;B;B;.
Vest4		0.35
MutPred		0.43		.;Gain of ubiquitination at K299 (P = 0.0797);.;.;
MVP		0.33
MPC		1.6
ClinPred		0.42	T
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-67885802;