chr3-48409685-C-T

Position:

• chr3-48409685-C-T

Variant summary

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

The NM_001130082.3(PLXNB1):​c.5825G>A​(p.Ser1942Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,626 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1942G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PLXNB1 NM_001130082.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.77

Genes affected

PLXNB1 (HGNC:9103): (plexin B1) Enables semaphorin receptor activity. Involved in several processes, including negative regulation of cell adhesion; regulation of cell shape; and semaphorin-plexin signaling pathway. Is integral component of plasma membrane. Part of semaphorin receptor complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLXNB1	NM_001130082.3	c.5825G>A	p.Ser1942Asn	missense_variant	33/38	ENST00000296440.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXNB1	ENST00000296440.11	c.5825G>A	p.Ser1942Asn	missense_variant	33/38	1	NM_001130082.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461626 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 727130

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Oct 03, 2023

The c.5825G>A (p.S1942N) alteration is located in exon 33 (coding exon 31) of the PLXNB1 gene. This alteration results from a G to A substitution at nucleotide position 5825, causing the serine (S) at amino acid position 1942 to be replaced by an asparagine (N). 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	0.16
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T;T;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.47	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.6	M;M;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.5	N;N;D
REVEL	Benign	0.18
Sift	Benign	0.059	T;T;T
Sift4G	Benign	0.085	T;T;T
Polyphen		0.80	P;P;D
Vest4		0.51
MutPred		0.63		Loss of catalytic residue at S1942 (P = 0.095);Loss of catalytic residue at S1942 (P = 0.095);.;
MVP		0.62
MPC		0.92
ClinPred		0.97	D
GERP RS		4.2
Varity_R		0.79
gMVP		0.60

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: chr3-48451093;