rs1557879

Variant names:

• chr5-9308427-A-G
• rs1557879
• NM_003966.3:c.270+9945T>C

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+9945T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,070 control chromosomes in the GnomAD database, including 1,610 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 (1610 hom., cov: 32)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751
• 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 (SAS) allele frequency at 95% confidence interval = 0.182 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+9945T>C		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+9945T>C		intron	N/A	ENSP00000371936.5	Q13591
	SEMA5A	ENST00000652226.1		c.270+9945T>C		intron	N/A	ENSP00000499013.1	Q13591
	SEMA5A	ENST00000897596.1		c.270+9945T>C		intron	N/A	ENSP00000567655.1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21436 AN: 151952 Hom.: 1602 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0795

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.141 AC: 21478 AN: 152070 Hom.: 1610 Cov.: 32 AF XY: 0.142 AC XY: 10546 AN XY: 74350

African (AFR) AF: 0.174 AC: 7229 AN: 41470

American (AMR) AF: 0.137 AC: 2100 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 435 AN: 3472

East Asian (EAS) AF: 0.0799 AC: 413 AN: 5168

South Asian (SAS) AF: 0.192 AC: 926 AN: 4814

European-Finnish (FIN) AF: 0.116 AC: 1232 AN: 10582

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8596 AN: 67972

Other (OTH) AF: 0.157 AC: 330 AN: 2108

Alfa AF: 0.129 Hom.: 517

Bravo AF: 0.141

Asia WGS AF: 0.140 AC: 486 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	1.4
DANN	Benign	0.21
PhyloP100		-0.75
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: rs1557879; hg19: chr5-9308539;