NM_003966.3:c.-175+36717A>G

Variant names:

• chr5-9508867-T-C
• rs421548
• NM_003966.3:c.-175+36717A>G

Variant summary

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

The NM_003966.3(SEMA5A):​c.-175+36717A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 152,230 control chromosomes in the GnomAD database, including 62,204 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 0.90 (62204 hom., cov: 32)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.18

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA5A	NM_003966.3	c.-175+36717A>G		intron_variant	Intron 1 of 22	ENST00000382496.10	NP_003957.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA5A	ENST00000382496.10	c.-175+36717A>G		intron_variant	Intron 1 of 22	1	NM_003966.3	ENSP00000371936.5
SEMA5A	ENST00000652226.1	c.-393+36717A>G		intron_variant	Intron 1 of 24			ENSP00000499013.1

Frequencies

GnomAD3 genomes AF: 0.903 AC: 137345 AN: 152112 Hom.: 62176 Cov.: 32

Gnomad AFR AF: 0.926

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.886

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.903

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.914

Gnomad OTH AF: 0.913

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

GnomAD4 genome AF: 0.903 AC: 137425 AN: 152230 Hom.: 62204 Cov.: 32 AF XY: 0.899 AC XY: 66909 AN XY: 74414

Gnomad4 AFR AF: 0.926 AC: 0.925608 AN: 0.925608

Gnomad4 AMR AF: 0.886 AC: 0.886069 AN: 0.886069

Gnomad4 ASJ AF: 0.916 AC: 0.916475 AN: 0.916475

Gnomad4 EAS AF: 0.670 AC: 0.670027 AN: 0.670027

Gnomad4 SAS AF: 0.818 AC: 0.817767 AN: 0.817767

Gnomad4 FIN AF: 0.903 AC: 0.903001 AN: 0.903001

Gnomad4 NFE AF: 0.914 AC: 0.914266 AN: 0.914266

Gnomad4 OTH AF: 0.904 AC: 0.904447 AN: 0.904447

Alfa AF: 0.915 Hom.: 27429

Bravo AF: 0.905

Asia WGS AF: 0.732 AC: 2544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.22
DANN	Benign	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

Publications

LitVar

Other links and lift over

dbSNP: rs421548; hg19: chr5-9508979;