5-9044475-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_003966.3(SEMA5A):c.3003C>T(p.His1001=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00219 in 1,613,982 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (23 hom.)
• Consequence: SEMA5A NM_003966.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.642

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 5-9044475-G-A is Benign according to our data. Variant chr5-9044475-G-A is described in ClinVar as [Benign]. Clinvar id is 782995.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.642 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA5A	NM_003966.3	c.3003C>T	p.His1001=	synonymous_variant	22/23	ENST00000382496.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA5A	ENST00000382496.10	c.3003C>T	p.His1001=	synonymous_variant	22/23	1	NM_003966.3	P1
	ENST00000506519.1	n.669+1198G>A		intron_variant, non_coding_transcript_variant		3
SEMA5A	ENST00000652226.1	c.3003C>T	p.His1001=	synonymous_variant	24/25			P1

Frequencies

GnomAD3 genomes AF: 0.00149 AC: 227 AN: 152104 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.00998

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00191

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00245 AC: 616 AN: 251468 Hom.: 3 AF XY: 0.00293 AC XY: 398 AN XY: 135910

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000925

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000653

Gnomad SAS exome AF: 0.0119

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.00174

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00226 AC: 3309 AN: 1461760 Hom.: 23 Cov.: 31 AF XY: 0.00259 AC XY: 1881 AN XY: 727170

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.00130

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000302

Gnomad4 SAS exome AF: 0.0120

Gnomad4 FIN exome AF: 0.000187

Gnomad4 NFE exome AF: 0.00183

Gnomad4 OTH exome AF: 0.00204

GnomAD4 genome AF: 0.00149 AC: 227 AN: 152222 Hom.: 1 Cov.: 32 AF XY: 0.00156 AC XY: 116 AN XY: 74398

Gnomad4 AFR AF: 0.000481

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.00999

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.00191

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.000991 Hom.: 0

Bravo AF: 0.00125

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	5.5
Dann	Benign	0.80

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: rs147519596; hg19: chr5-9044587; COSMIC: COSV66787578;