NM_003966.3:c.270+12759G>A

Variant names:

• chr5-9305613-C-T
• rs12658266
• NM_003966.3:c.270+12759G>A

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+12759G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 151,044 control chromosomes in the GnomAD database, including 38,010 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 0.68 (38010 hom., cov: 27)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA5A	NM_003966.3	c.270+12759G>A		intron_variant	Intron 5 of 22	ENST00000382496.10	NP_003957.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA5A	ENST00000382496.10	c.270+12759G>A		intron_variant	Intron 5 of 22	1	NM_003966.3	ENSP00000371936.5
SEMA5A	ENST00000652226.1	c.270+12759G>A		intron_variant	Intron 7 of 24			ENSP00000499013.1
SEMA5A	ENST00000513968.4	c.270+12759G>A		intron_variant	Intron 4 of 7	5		ENSP00000421961.1
SEMA5A	ENST00000509486.2	n.347+12759G>A		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.681 AC: 102772 AN: 150930 Hom.: 38017 Cov.: 27

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.713

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

GnomAD4 genome AF: 0.681 AC: 102789 AN: 151044 Hom.: 38010 Cov.: 27 AF XY: 0.680 AC XY: 50175 AN XY: 73736

African (AFR) AF: 0.366 AC: 15036 AN: 41046

American (AMR) AF: 0.710 AC: 10745 AN: 15136

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 2882 AN: 3464

East Asian (EAS) AF: 0.729 AC: 3738 AN: 5130

South Asian (SAS) AF: 0.740 AC: 3520 AN: 4754

European-Finnish (FIN) AF: 0.806 AC: 8372 AN: 10384

Middle Eastern (MID) AF: 0.740 AC: 216 AN: 292

European-Non Finnish (NFE) AF: 0.826 AC: 56076 AN: 67848

Other (OTH) AF: 0.717 AC: 1492 AN: 2082

Alfa AF: 0.720 Hom.: 5414

Bravo AF: 0.657

Asia WGS AF: 0.689 AC: 2395 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.94
DANN	Benign	0.51
PhyloP100		-1.0
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: rs12658266; hg19: chr5-9305725;