1-67430249-C-G

Position:

• chr1-67430249-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001018069.2(SERBP1):​c.52G>C​(p.Asp18His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SERBP1 NM_001018069.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.67

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3774616).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERBP1	NM_001018069.2	c.52G>C	p.Asp18His	missense_variant	1/8	ENST00000361219.11
SERBP1	NM_001018067.2	c.52G>C	p.Asp18His	missense_variant	1/8
SERBP1	NM_001018068.2	c.52G>C	p.Asp18His	missense_variant	1/8
SERBP1	NM_015640.4	c.52G>C	p.Asp18His	missense_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERBP1	ENST00000361219.11	c.52G>C	p.Asp18His	missense_variant	1/8	1	NM_001018069.2
SERBP1	ENST00000370995.6	c.52G>C	p.Asp18His	missense_variant	1/8	1		P3
SERBP1	ENST00000370990.5	c.52G>C	p.Asp18His	missense_variant	1/8	1		A1
SERBP1	ENST00000370994.8	c.52G>C	p.Asp18His	missense_variant	1/8	1		A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Dec 13, 2022

The c.52G>C (p.D18H) alteration is located in exon 1 (coding exon 1) of the SERBP1 gene. This alteration results from a G to C substitution at nucleotide position 52, causing the aspartic acid (D) at amino acid position 18 to be replaced by a histidine (H). 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	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	29
DANN	Uncertain	0.99
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.76	T;T;T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.38	T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.4	L;L;L;L
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.6	N;N;N;N
REVEL	Benign	0.23
Sift	Benign	0.53	T;T;T;T
Sift4G	Benign	0.64	T;T;T;T
Polyphen		1.0	.;D;D;.
Vest4		0.43
MutPred		0.40		Gain of catalytic residue at R16 (P = 0.0938);Gain of catalytic residue at R16 (P = 0.0938);Gain of catalytic residue at R16 (P = 0.0938);Gain of catalytic residue at R16 (P = 0.0938);
MVP		0.78
MPC		2.0
ClinPred		0.90	D
GERP RS		4.0
Varity_R		0.50
gMVP		0.57

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: chr1-67895932;