5-9322365-G-T

Position:

• chr5-9322365-G-T

Variant summary

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

The NM_003966.3(SEMA5A):​c.225-3948C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 151,636 control chromosomes in the GnomAD database, including 10,276 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 0.31 (10276 hom., cov: 31)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.67

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]

SEMA5A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA5A	NM_003966.3	c.225-3948C>A		intron_variant		ENST00000382496.10	NP_003957.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA5A	ENST00000382496.10	c.225-3948C>A		intron_variant		1	NM_003966.3	ENSP00000371936.5
SEMA5A	ENST00000652226.1	c.225-3948C>A		intron_variant				ENSP00000499013.1
SEMA5A	ENST00000513968.4	c.225-3948C>A		intron_variant		5		ENSP00000421961.1
SEMA5A	ENST00000509486.2	n.302-3948C>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46589 AN: 151518 Hom.: 10250 Cov.: 31

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.308 AC: 46678 AN: 151636 Hom.: 10276 Cov.: 31 AF XY: 0.308 AC XY: 22803 AN XY: 74080

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.272

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.283

Alfa AF: 0.248 Hom.: 868

Bravo AF: 0.331

Asia WGS AF: 0.313 AC: 1088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.021
DANN	Benign	0.54

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: rs3822789; hg19: chr5-9322477;