5-9507512-C-T

Variant names:

• chr5-9507512-C-T
• rs369459
• NM_003966.3:c.-175+38072G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003966.3(SEMA5A):​c.-175+38072G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 152,218 control chromosomes in the GnomAD database, including 60,540 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 0.89 (60540 hom., cov: 32)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003966.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA5A	NM_003966.3	MANE Select	c.-175+38072G>A		intron	N/A	NP_003957.2	X5DR95

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA5A	ENST00000382496.10	TSL:1 MANE Select	c.-175+38072G>A		intron	N/A	ENSP00000371936.5	Q13591
	SEMA5A	ENST00000652226.1		c.-393+38072G>A		intron	N/A	ENSP00000499013.1	Q13591
	SEMA5A	ENST00000897596.1		c.-248+38072G>A		intron	N/A	ENSP00000567655.1

Frequencies

GnomAD3 genomes AF: 0.890 AC: 135440 AN: 152100 Hom.: 60514 Cov.: 32

Gnomad AFR AF: 0.885

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.917

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.902

Gnomad MID AF: 0.939

Gnomad NFE AF: 0.914

Gnomad OTH AF: 0.901

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

GnomAD4 genome AF: 0.890 AC: 135517 AN: 152218 Hom.: 60540 Cov.: 32 AF XY: 0.886 AC XY: 65985 AN XY: 74442

African (AFR) AF: 0.884 AC: 36725 AN: 41522

American (AMR) AF: 0.884 AC: 13511 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.917 AC: 3183 AN: 3472

East Asian (EAS) AF: 0.646 AC: 3342 AN: 5170

South Asian (SAS) AF: 0.819 AC: 3947 AN: 4822

European-Finnish (FIN) AF: 0.902 AC: 9579 AN: 10614

Middle Eastern (MID) AF: 0.949 AC: 277 AN: 292

European-Non Finnish (NFE) AF: 0.914 AC: 62179 AN: 68012

Other (OTH) AF: 0.893 AC: 1887 AN: 2112

Alfa AF: 0.907 Hom.: 170620

Bravo AF: 0.891

Asia WGS AF: 0.717 AC: 2492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.3
DANN	Benign	0.80
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs369459; hg19: chr5-9507624;