1-45642442-G-A

Variant names:

• chr1-45642442-G-A
• NM_021639.5:c.535C>T

Variant summary

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

The NM_021639.5(GPBP1L1):​c.535C>T​(p.Pro179Ser) variant causes a missense change involving the alteration of a 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: 32)
• Consequence: GPBP1L1 NM_021639.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.22

Genes affected

GPBP1L1 (HGNC:28843): (GC-rich promoter binding protein 1 like 1) Predicted to enable DNA binding activity and RNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be active in 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=0.31910688).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPBP1L1	NM_021639.5	c.535C>T	p.Pro179Ser	missense_variant	Exon 7 of 13	ENST00000355105.8	NP_067652.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPBP1L1	ENST00000355105.8	c.535C>T	p.Pro179Ser	missense_variant	Exon 7 of 13	1	NM_021639.5	ENSP00000347224.3
GPBP1L1	ENST00000290795.7	c.535C>T	p.Pro179Ser	missense_variant	Exon 6 of 12	5		ENSP00000290795.3
GPBP1L1	ENST00000498128.1	n.402C>T		non_coding_transcript_exon_variant	Exon 3 of 4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.535C>T (p.P179S) alteration is located in exon 7 (coding exon 4) of the GPBP1L1 gene. This alteration results from a C to T substitution at nucleotide position 535, causing the proline (P) at amino acid position 179 to be replaced by a serine (S). 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	0.23
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.063	T;T
Eigen	Uncertain	0.60
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	.;D
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	2.0	M;M
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.13
Sift	Benign	0.083	T;T
Sift4G	Benign	0.45	T;T
Polyphen		0.74	P;P
Vest4		0.52
MutPred		0.20		Gain of catalytic residue at P179 (P = 0.0328);Gain of catalytic residue at P179 (P = 0.0328);
MVP		0.45
MPC		0.42
ClinPred		0.77	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.049
gMVP		0.13

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: chr1-46108114;