rs3797993

Variant names:

• chr5-9357452-C-T
• rs3797993
• NM_003966.3:c.125-19640G>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.125-19640G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 152,230 control chromosomes in the GnomAD database, including 87 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 0.016 (87 hom., cov: 33)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.542
• Publications: 0 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.123 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.125-19640G>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.125-19640G>A		intron	N/A	ENSP00000371936.5	Q13591
	SEMA5A	ENST00000652226.1		c.125-19640G>A		intron	N/A	ENSP00000499013.1	Q13591
	SEMA5A	ENST00000897596.1		c.125-19640G>A		intron	N/A	ENSP00000567655.1

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 2503 AN: 152114 Hom.: 88 Cov.: 33

Gnomad AFR AF: 0.00702

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0464

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.0193

Gnomad FIN AF: 0.0471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00288

Gnomad OTH AF: 0.0162

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

GnomAD4 genome AF: 0.0164 AC: 2499 AN: 152230 Hom.: 87 Cov.: 33 AF XY: 0.0196 AC XY: 1461 AN XY: 74420

African (AFR) AF: 0.00700 AC: 291 AN: 41546

American (AMR) AF: 0.0463 AC: 707 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.131 AC: 680 AN: 5172

South Asian (SAS) AF: 0.0195 AC: 94 AN: 4816

European-Finnish (FIN) AF: 0.0471 AC: 499 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00288 AC: 196 AN: 68026

Other (OTH) AF: 0.0151 AC: 32 AN: 2116

Alfa AF: 0.00985 Hom.: 2

Bravo AF: 0.0192

Asia WGS AF: 0.0700 AC: 242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.64
PhyloP100		-0.54
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: rs3797993; hg19: chr5-9357564;