rs571826

Variant names:

• chr5-9460341-G-A
• rs571826
• NM_003966.3:c.-174-22489C>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.-174-22489C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 151,116 control chromosomes in the GnomAD database, including 2,547 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 0.15 (2547 hom., cov: 33)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109
• 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 = 0.314 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.-174-22489C>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.-174-22489C>T		intron	N/A	ENSP00000371936.5	Q13591
	SEMA5A	ENST00000652226.1		c.-392-22489C>T		intron	N/A	ENSP00000499013.1	Q13591
	SEMA5A	ENST00000897596.1		c.-247-22489C>T		intron	N/A	ENSP00000567655.1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22592 AN: 151002 Hom.: 2530 Cov.: 33

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.0292

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0789

Gnomad EAS AF: 0.0425

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0926

Gnomad MID AF: 0.0617

Gnomad NFE AF: 0.0835

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.150 AC: 22666 AN: 151116 Hom.: 2547 Cov.: 33 AF XY: 0.148 AC XY: 10922 AN XY: 73790

African (AFR) AF: 0.318 AC: 13189 AN: 41414

American (AMR) AF: 0.104 AC: 1573 AN: 15154

Ashkenazi Jewish (ASJ) AF: 0.0789 AC: 271 AN: 3436

East Asian (EAS) AF: 0.0424 AC: 219 AN: 5170

South Asian (SAS) AF: 0.105 AC: 467 AN: 4466

European-Finnish (FIN) AF: 0.0926 AC: 977 AN: 10546

Middle Eastern (MID) AF: 0.0559 AC: 16 AN: 286

European-Non Finnish (NFE) AF: 0.0835 AC: 5653 AN: 67698

Other (OTH) AF: 0.132 AC: 276 AN: 2090

Alfa AF: 0.132 Hom.: 197

Bravo AF: 0.154

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.35
PhyloP100		-0.11
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: rs571826; hg19: chr5-9460453;