5-9154547-G-C

Position:

• chr5-9154547-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003966.3(SEMA5A):​c.1422C>G​(p.Gly474Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 1,612,488 control chromosomes in the GnomAD database, including 211,362 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (14325 hom., cov: 30)
  • Exomes 𝑓: 0.51 (197037 hom.)
• Consequence: SEMA5A NM_003966.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.74

Genes affected

SEMA5A (HGNC:10736): (semaphorin 5A) This gene belongs to the semaphorin gene family that encodes membrane proteins containing a semaphorin domain and several thrombospondin type-1 repeats. Members of this family are involved in axonal guidance during neural development. This gene has been implicated as an autism susceptibility gene.[provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 5-9154547-G-C is Benign according to our data. Variant chr5-9154547-G-C is described in ClinVar as [Benign]. Clinvar id is 1292005.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.74 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA5A	NM_003966.3	c.1422C>G	p.Gly474Gly	synonymous_variant	12/23	ENST00000382496.10	NP_003957.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA5A	ENST00000382496.10	c.1422C>G	p.Gly474Gly	synonymous_variant	12/23	1	NM_003966.3	ENSP00000371936.5
SEMA5A	ENST00000652226.1	c.1422C>G	p.Gly474Gly	synonymous_variant	14/25			ENSP00000499013.1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59288 AN: 151724 Hom.: 14334 Cov.: 30

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.423

GnomAD3 exomes AF: 0.424 AC: 106496 AN: 251056 Hom.: 25655 AF XY: 0.434 AC XY: 58829 AN XY: 135700

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.268

Gnomad ASJ exome AF: 0.580

Gnomad EAS exome AF: 0.249

Gnomad SAS exome AF: 0.331

Gnomad FIN exome AF: 0.469

Gnomad NFE exome AF: 0.547

Gnomad OTH exome AF: 0.470

GnomAD4 exome AF: 0.507 AC: 741061 AN: 1460644 Hom.: 197037 Cov.: 61 AF XY: 0.504 AC XY: 366063 AN XY: 726644

Gnomad4 AFR exome AF: 0.0963

Gnomad4 AMR exome AF: 0.278

Gnomad4 ASJ exome AF: 0.581

Gnomad4 EAS exome AF: 0.238

Gnomad4 SAS exome AF: 0.334

Gnomad4 FIN exome AF: 0.472

Gnomad4 NFE exome AF: 0.554

Gnomad4 OTH exome AF: 0.481

GnomAD4 genome AF: 0.390 AC: 59259 AN: 151844 Hom.: 14325 Cov.: 30 AF XY: 0.385 AC XY: 28564 AN XY: 74174

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.581

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.419

Alfa AF: 0.508 Hom.: 6739

Bravo AF: 0.370

Asia WGS AF: 0.243 AC: 847 AN: 3478

EpiCase AF: 0.548

EpiControl AF: 0.560

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 26, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	3.4
DANN	Benign	0.61

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: rs1806151; hg19: chr5-9154659; COSMIC: COSV66787217;