5-9490307-T-C

Position:

• chr5-9490307-T-C

Variant summary

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

The NM_003966.3(SEMA5A):​c.-174-52455A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0614 in 152,266 control chromosomes in the GnomAD database, including 375 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 0.061 (375 hom., cov: 32)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA5A	NM_003966.3	c.-174-52455A>G		intron_variant		ENST00000382496.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA5A	ENST00000382496.10	c.-174-52455A>G		intron_variant		1	NM_003966.3	P1
SEMA5A	ENST00000652226.1	c.-392-52455A>G		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.0614 AC: 9337 AN: 152148 Hom.: 370 Cov.: 32

Gnomad AFR AF: 0.0157

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0675

Gnomad ASJ AF: 0.0741

Gnomad EAS AF: 0.0418

Gnomad SAS AF: 0.0989

Gnomad FIN AF: 0.0924

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0818

Gnomad OTH AF: 0.0589

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

GnomAD4 genome AF: 0.0614 AC: 9350 AN: 152266 Hom.: 375 Cov.: 32 AF XY: 0.0620 AC XY: 4616 AN XY: 74440

Gnomad4 AFR AF: 0.0157

Gnomad4 AMR AF: 0.0673

Gnomad4 ASJ AF: 0.0741

Gnomad4 EAS AF: 0.0417

Gnomad4 SAS AF: 0.0988

Gnomad4 FIN AF: 0.0924

Gnomad4 NFE AF: 0.0818

Gnomad4 OTH AF: 0.0668

Alfa AF: 0.0485 Hom.: 50

Bravo AF: 0.0538

Asia WGS AF: 0.123 AC: 430 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.086
DANN	Benign	0.85

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: rs3777359; hg19: chr5-9490419;