chr5-9299126-G-A

Position:

• chr5-9299126-G-A

Variant summary

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

The NM_003966.3(SEMA5A):​c.270+19246C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,024 control chromosomes in the GnomAD database, including 1,599 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 0.14 (1599 hom., cov: 32)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.444

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA5A	NM_003966.3	c.270+19246C>T		intron_variant		ENST00000382496.10	NP_003957.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA5A	ENST00000382496.10	c.270+19246C>T		intron_variant		1	NM_003966.3	ENSP00000371936	P1
SEMA5A	ENST00000513968.4	c.270+19246C>T		intron_variant		5		ENSP00000421961
SEMA5A	ENST00000652226.1	c.270+19246C>T		intron_variant				ENSP00000499013	P1
SEMA5A	ENST00000509486.2	n.348-18319C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21276 AN: 151906 Hom.: 1594 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0778

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.140 AC: 21311 AN: 152024 Hom.: 1599 Cov.: 32 AF XY: 0.141 AC XY: 10481 AN XY: 74304

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.0782

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.153

Alfa AF: 0.135 Hom.: 681

Bravo AF: 0.140

Asia WGS AF: 0.140 AC: 486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.3
DANN	Benign	0.68

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: rs13360783; hg19: chr5-9299238;