GPBP1L1 p.Lys148Asn

Variant names:

• chr1-45654576-C-A
• NM_021639.5:c.444G>T
• GPBP1L1 p.Lys148Asn

Your query was ambiguous. Multiple possible variants found:

• chr1-45654576-C-A
• chr1-45654576-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_021639.5(GPBP1L1):​c.444G>T​(p.Lys148Asn) 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. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPBP1L1 NM_021639.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46
• Publications: 0 publications found

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]

ENSG00000306015 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37677062).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021639.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPBP1L1	NM_021639.5	MANE Select	c.444G>T	p.Lys148Asn	missense	Exon 6 of 13	NP_067652.1	Q9HC44
	GPBP1L1	NM_001439214.1		c.444G>T	p.Lys148Asn	missense	Exon 5 of 12	NP_001426143.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPBP1L1	ENST00000355105.8	TSL:1 MANE Select	c.444G>T	p.Lys148Asn	missense	Exon 6 of 13	ENSP00000347224.3	Q9HC44
	GPBP1L1	ENST00000290795.7	TSL:5	c.444G>T	p.Lys148Asn	missense	Exon 5 of 12	ENSP00000290795.3	Q9HC44
	GPBP1L1	ENST00000871064.1		c.444G>T	p.Lys148Asn	missense	Exon 5 of 12	ENSP00000541123.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.053
Eigen_PC	Benign	0.052
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.5
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.11
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.074	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.46
gMVP		0.18
Mutation Taster		=68/32	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-46120248;