5-17275514-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006317.5(BASP1):c.298C>T(p.Pro100Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000465 in 1,290,618 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: 0.0000046 (0 hom.)
• Consequence: BASP1 NM_006317.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.25

Genes affected

BASP1 (HGNC:957): (brain abundant membrane attached signal protein 1) This gene encodes a membrane bound protein with several transient phosphorylation sites and PEST motifs. Conservation of proteins with PEST sequences among different species supports their functional significance. PEST sequences typically occur in proteins with high turnover rates. Immunological characteristics of this protein are species specific. This protein also undergoes N-terminal myristoylation. Alternative splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Oct 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15445665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BASP1	NM_006317.5	c.298C>T	p.Pro100Ser	missense_variant	2/2	ENST00000322611.4
BASP1	NM_001271606.2	c.298C>T	p.Pro100Ser	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BASP1	ENST00000322611.4	c.298C>T	p.Pro100Ser	missense_variant	2/2	1	NM_006317.5	P1
BASP1	ENST00000616743.1	c.298C>T	p.Pro100Ser	missense_variant	2/2	3		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000222 AC: 1 AN: 45026 Hom.: 0 AF XY: 0.0000433 AC XY: 1 AN XY: 23110

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.0000748

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000465 AC: 6 AN: 1290618 Hom.: 0 Cov.: 32 AF XY: 0.00000477 AC XY: 3 AN XY: 629020

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: 0.0000319

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000193

Gnomad4 OTH exome AF: 0.0000189

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Oct 16, 2023

The c.298C>T (p.P100S) alteration is located in exon 2 (coding exon 1) of the BASP1 gene. This alteration results from a C to T substitution at nucleotide position 298, causing the proline (P) at amino acid position 100 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	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
Cadd	Benign	17
Dann	Benign	0.95
DEOGEN2	Uncertain	0.42	T;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.68	T;.
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.0	M;M
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.84	D
Sift4G	Uncertain	0.054	T;T
Polyphen		0.025	B;B
Vest4		0.13
MutPred		0.51		Loss of catalytic residue at P100 (P = 0.0018);Loss of catalytic residue at P100 (P = 0.0018);
MVP		0.12
MPC		0.44
ClinPred		0.21	T
GERP RS		3.3
Varity_R		0.19
gMVP		0.17

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

Other links and lift over

dbSNP: rs1386047183; hg19: chr5-17275623;