NM_020911.2:c.5574C>A

Variant names:

• chr7-132133064-G-T
• rs190064899
• NM_020911.2:c.5574C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_020911.2(PLXNA4):​c.5574C>A​(p.Gly1858Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0032 in 1,613,990 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0024 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (16 hom.)
• Consequence: PLXNA4 NM_020911.2 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.51
• Publications: 1 publications found

Genes affected

PLXNA4 (HGNC:9102): (plexin A4) Predicted to enable semaphorin receptor activity. Predicted to be involved in several processes, including axon guidance; positive regulation of axonogenesis; and regulation of GTPase activity. Predicted to act upstream of or within several processes, including nervous system development; regulation of axon extension involved in axon guidance; and regulation of negative chemotaxis. Predicted to be located in plasma membrane. Predicted to be part of semaphorin receptor complex. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 7-132133064-G-T is Benign according to our data. Variant chr7-132133064-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3041340.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.51 with no splicing effect.
• BS2: High AC in GnomAd4 at 370 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020911.2. 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
	PLXNA4	NM_020911.2	MANE Select	c.5574C>A	p.Gly1858Gly	synonymous	Exon 31 of 32	NP_065962.1	Q9HCM2-1
	PLXNA4	NM_001393897.1		c.5574C>A	p.Gly1858Gly	synonymous	Exon 31 of 32	NP_001380826.1	Q9HCM2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXNA4	ENST00000321063.9	TSL:5 MANE Select	c.5574C>A	p.Gly1858Gly	synonymous	Exon 31 of 32	ENSP00000323194.4	Q9HCM2-1
	PLXNA4	ENST00000359827.7	TSL:5	c.5574C>A	p.Gly1858Gly	synonymous	Exon 31 of 32	ENSP00000352882.3	Q9HCM2-1
	PLXNA4	ENST00000948949.1		c.5574C>A	p.Gly1858Gly	synonymous	Exon 32 of 33	ENSP00000619008.1

Frequencies

GnomAD3 genomes AF: 0.00243 AC: 370 AN: 152162 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00387

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00331

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00235 AC: 586 AN: 249068 AF XY: 0.00255

Gnomad AFR exome AF: 0.000646

Gnomad AMR exome AF: 0.00212

Gnomad ASJ exome AF: 0.00189

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00381

Gnomad NFE exome AF: 0.00297

Gnomad OTH exome AF: 0.00281

GnomAD4 exome AF: 0.00328 AC: 4797 AN: 1461710 Hom.: 16 Cov.: 30 AF XY: 0.00323 AC XY: 2346 AN XY: 727152

African (AFR) AF: 0.000478 AC: 16 AN: 33476

American (AMR) AF: 0.00183 AC: 82 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00207 AC: 54 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00182 AC: 157 AN: 86220

European-Finnish (FIN) AF: 0.00333 AC: 178 AN: 53412

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.00375 AC: 4166 AN: 1111926

Other (OTH) AF: 0.00237 AC: 143 AN: 60388

GnomAD4 genome AF: 0.00243 AC: 370 AN: 152280 Hom.: 2 Cov.: 32 AF XY: 0.00222 AC XY: 165 AN XY: 74456

African (AFR) AF: 0.000650 AC: 27 AN: 41562

American (AMR) AF: 0.00386 AC: 59 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4820

European-Finnish (FIN) AF: 0.00387 AC: 41 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00331 AC: 225 AN: 68034

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.00247 Hom.: 1

Bravo AF: 0.00203

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00305

EpiControl AF: 0.00261

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PLXNA4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.5
DANN	Benign	0.61
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism

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: rs190064899; hg19: chr7-131817823;