rs1347003

Positions:

• chr3-127013204-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032242.4(PLXNA1):​c.2314-816T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 152,058 control chromosomes in the GnomAD database, including 15,147 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (15147 hom., cov: 33)
• Consequence: PLXNA1 NM_032242.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.451

Genes affected

PLXNA1 (HGNC:9099): (plexin A1) Predicted to enable semaphorin receptor activity. Predicted to be involved in several processes, including generation of neurons; regulation of GTPase activity; and regulation of cell shape. Predicted to act upstream of or within dichotomous subdivision of terminal units involved in salivary gland branching; neuron projection morphogenesis; and regulation of smooth muscle cell migration. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLXNA1	NM_032242.4	c.2314-816T>C		intron_variant		ENST00000393409.3	NP_115618.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLXNA1	ENST00000393409.3	c.2314-816T>C		intron_variant		1	NM_032242.4	ENSP00000377061	P1

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63679 AN: 151942 Hom.: 15121 Cov.: 33

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.402

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.419 AC: 63754 AN: 152058 Hom.: 15147 Cov.: 33 AF XY: 0.417 AC XY: 31004 AN XY: 74344

Gnomad4 AFR AF: 0.660

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.400

Alfa AF: 0.328 Hom.: 13206

Bravo AF: 0.434

Asia WGS AF: 0.423 AC: 1472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.51

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: rs1347003; hg19: chr3-126732047;