chr5-9307315-T-A

Variant names:

• chr5-9307315-T-A
• rs3777320
• NM_003966.3:c.270+11057A>T

Variant summary

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

The NM_003966.3(SEMA5A):​c.270+11057A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,134 control chromosomes in the GnomAD database, including 2,318 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 0.17 (2318 hom., cov: 32)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.229 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.270+11057A>T		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.270+11057A>T		intron	N/A	ENSP00000371936.5	Q13591
	SEMA5A	ENST00000652226.1		c.270+11057A>T		intron	N/A	ENSP00000499013.1	Q13591
	SEMA5A	ENST00000897596.1		c.270+11057A>T		intron	N/A	ENSP00000567655.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25446 AN: 152016 Hom.: 2314 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.167 AC: 25477 AN: 152134 Hom.: 2318 Cov.: 32 AF XY: 0.171 AC XY: 12746 AN XY: 74372

African (AFR) AF: 0.209 AC: 8663 AN: 41524

American (AMR) AF: 0.194 AC: 2959 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 435 AN: 3470

East Asian (EAS) AF: 0.240 AC: 1236 AN: 5148

South Asian (SAS) AF: 0.218 AC: 1049 AN: 4818

European-Finnish (FIN) AF: 0.164 AC: 1736 AN: 10590

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8801 AN: 67992

Other (OTH) AF: 0.178 AC: 377 AN: 2114

Alfa AF: 0.150 Hom.: 224

Bravo AF: 0.171

Asia WGS AF: 0.230 AC: 799 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.69
DANN	Benign	0.45
PhyloP100		-0.40
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: rs3777320; hg19: chr5-9307427;