rs433755

Variant names:

• chr5-9474834-A-C
• rs433755
• NM_003966.3:c.-174-36982T>G

Your query was ambiguous. Multiple possible variants found:

• chr5-9474834-A-C
• chr5-9474834-A-G
• chr5-9474834-A-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.-174-36982T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 152,070 control chromosomes in the GnomAD database, including 21,096 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 0.52 (21096 hom., cov: 33)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149
• Publications: 8 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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.543 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.-174-36982T>G		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.-174-36982T>G		intron	N/A	ENSP00000371936.5	Q13591
	SEMA5A	ENST00000652226.1		c.-392-36982T>G		intron	N/A	ENSP00000499013.1	Q13591
	SEMA5A	ENST00000897596.1		c.-247-36982T>G		intron	N/A	ENSP00000567655.1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 79038 AN: 151948 Hom.: 21078 Cov.: 33

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.520 AC: 79091 AN: 152070 Hom.: 21096 Cov.: 33 AF XY: 0.517 AC XY: 38424 AN XY: 74346

African (AFR) AF: 0.530 AC: 21988 AN: 41472

American (AMR) AF: 0.521 AC: 7964 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1656 AN: 3472

East Asian (EAS) AF: 0.142 AC: 733 AN: 5168

South Asian (SAS) AF: 0.437 AC: 2106 AN: 4822

European-Finnish (FIN) AF: 0.536 AC: 5665 AN: 10560

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.548 AC: 37231 AN: 67968

Other (OTH) AF: 0.512 AC: 1081 AN: 2112

Alfa AF: 0.535 Hom.: 42357

Bravo AF: 0.516

Asia WGS AF: 0.341 AC: 1190 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	1.9
DANN	Benign	0.61
PhyloP100		-0.15
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: rs433755; hg19: chr5-9474946;