5-9322365-G-T

Variant names:

• chr5-9322365-G-T
• rs3822789
• NM_003966.3:c.225-3948C>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.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
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.618 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.225-3948C>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.225-3948C>A		intron	N/A	ENSP00000371936.5	Q13591
	SEMA5A	ENST00000652226.1		c.225-3948C>A		intron	N/A	ENSP00000499013.1	Q13591
	SEMA5A	ENST00000897596.1		c.225-3948C>A		intron	N/A	ENSP00000567655.1

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

African (AFR) AF: 0.624 AC: 25728 AN: 41238

American (AMR) AF: 0.286 AC: 4348 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 545 AN: 3470

East Asian (EAS) AF: 0.272 AC: 1393 AN: 5128

South Asian (SAS) AF: 0.260 AC: 1246 AN: 4788

European-Finnish (FIN) AF: 0.174 AC: 1832 AN: 10546

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10716 AN: 67942

Other (OTH) AF: 0.283 AC: 595 AN: 2102

Alfa AF: 0.250 Hom.: 1995

Bravo AF: 0.331

Asia WGS AF: 0.313 AC: 1088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.021
DANN	Benign	0.54
PhyloP100		-2.7
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: rs3822789; hg19: chr5-9322477;