NM_003966.3:c.-175+35560A>G

Variant names:

• chr5-9510024-T-C
• rs268478
• NM_003966.3:c.-175+35560A>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+35560A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.906 in 152,204 control chromosomes in the GnomAD database, including 62,624 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 0.91 (62624 hom., cov: 32)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660
• Publications: 2 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]

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 = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA5A	NM_003966.3	c.-175+35560A>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+35560A>G		intron_variant	Intron 1 of 22	1	NM_003966.3	ENSP00000371936.5
SEMA5A	ENST00000652226.1	c.-393+35560A>G		intron_variant	Intron 1 of 24			ENSP00000499013.1

Frequencies

GnomAD3 genomes AF: 0.906 AC: 137831 AN: 152086 Hom.: 62597 Cov.: 32

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.901

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.904

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.915

Gnomad OTH AF: 0.912

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

GnomAD4 genome AF: 0.906 AC: 137908 AN: 152204 Hom.: 62624 Cov.: 32 AF XY: 0.903 AC XY: 67162 AN XY: 74402

African (AFR) AF: 0.927 AC: 38499 AN: 41528

American (AMR) AF: 0.901 AC: 13787 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 3177 AN: 3470

East Asian (EAS) AF: 0.705 AC: 3641 AN: 5168

South Asian (SAS) AF: 0.820 AC: 3942 AN: 4810

European-Finnish (FIN) AF: 0.904 AC: 9575 AN: 10592

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.915 AC: 62214 AN: 68018

Other (OTH) AF: 0.904 AC: 1908 AN: 2110

Alfa AF: 0.911 Hom.: 9934

Bravo AF: 0.909

Asia WGS AF: 0.744 AC: 2586 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	7.6
DANN	Benign	0.66
PhyloP100		-0.066
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs268478; hg19: chr5-9510136;