rs1347003

Variant names:

• chr3-127013204-T-C
• rs1347003
• NM_032242.4:c.2314-816T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

PLXNA1 Gene-Disease associations (from GenCC):

• Dworschak-Punetha neurodevelopmental syndrome

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032242.4. 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
	PLXNA1	NM_032242.4	MANE Select	c.2314-816T>C		intron	N/A	NP_115618.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXNA1	ENST00000393409.3	TSL:1 MANE Select	c.2314-816T>C		intron	N/A	ENSP00000377061.2	Q9UIW2

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

African (AFR) AF: 0.660 AC: 27362 AN: 41458

American (AMR) AF: 0.367 AC: 5617 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1152 AN: 3472

East Asian (EAS) AF: 0.426 AC: 2199 AN: 5156

South Asian (SAS) AF: 0.392 AC: 1893 AN: 4824

European-Finnish (FIN) AF: 0.309 AC: 3265 AN: 10578

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 20984 AN: 67958

Other (OTH) AF: 0.400 AC: 846 AN: 2114

Alfa AF: 0.353 Hom.: 27064

Bravo AF: 0.434

Asia WGS AF: 0.423 AC: 1472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.51
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1347003; hg19: chr3-126732047;