chr5-17275883-G-C

Position:

• chr5-17275883-G-C

Variant summary

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

The ENST00000322611.4(BASP1):​c.667G>C​(p.Val223Leu) 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. 15/21 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)
• Consequence: BASP1 ENST00000322611.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.71

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=0.21071476).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BASP1	NM_006317.5	c.667G>C	p.Val223Leu	missense_variant	2/2	ENST00000322611.4	NP_006308.3
BASP1	NM_001271606.2	c.667G>C	p.Val223Leu	missense_variant	2/2		NP_001258535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BASP1	ENST00000322611.4	c.667G>C	p.Val223Leu	missense_variant	2/2	1	NM_006317.5	ENSP00000319281	P1
BASP1	ENST00000616743.1	c.667G>C	p.Val223Leu	missense_variant	2/2	3		ENSP00000482066	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Feb 06, 2024

The c.667G>C (p.V223L) alteration is located in exon 2 (coding exon 1) of the BASP1 gene. This alteration results from a G to C substitution at nucleotide position 667, causing the valine (V) at amino acid position 223 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	0.26
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.42	T;T
Eigen	Benign	0.098
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.80	T;.
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.8	L;L
MutationTaster	Benign	0.91	D
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.1	.;N
REVEL	Benign	0.076
Sift	Uncertain	0.022	.;D
Sift4G	Benign	0.090	T;T
Polyphen		0.76	P;P
Vest4		0.16
MutPred		0.63		Loss of methylation at K226 (P = 0.0923);Loss of methylation at K226 (P = 0.0923);
MVP		0.10
MPC		1.0
ClinPred		0.70	D
GERP RS		2.9
Varity_R		0.080
gMVP		0.094

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: chr5-17275992;