rs3777312

Variant names:

• chr5-9301384-C-T
• rs3777312
• NM_003966.3:c.270+16988G>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+16988G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,152 control chromosomes in the GnomAD database, including 1,577 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 0.14 (1577 hom., cov: 32)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA5A	NM_003966.3	c.270+16988G>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+16988G>A		intron_variant	Intron 5 of 22	1	NM_003966.3	ENSP00000371936.5
SEMA5A	ENST00000652226.1	c.270+16988G>A		intron_variant	Intron 7 of 24			ENSP00000499013.1
SEMA5A	ENST00000513968.4	c.270+16988G>A		intron_variant	Intron 4 of 7	5		ENSP00000421961.1
SEMA5A	ENST00000509486.2	n.347+16988G>A		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21192 AN: 152034 Hom.: 1572 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0788

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.140 AC: 21226 AN: 152152 Hom.: 1577 Cov.: 32 AF XY: 0.140 AC XY: 10440 AN XY: 74392

African (AFR) AF: 0.169 AC: 6990 AN: 41478

American (AMR) AF: 0.137 AC: 2088 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 435 AN: 3472

East Asian (EAS) AF: 0.0792 AC: 410 AN: 5178

South Asian (SAS) AF: 0.193 AC: 929 AN: 4818

European-Finnish (FIN) AF: 0.117 AC: 1239 AN: 10592

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8588 AN: 68004

Other (OTH) AF: 0.155 AC: 328 AN: 2114

Alfa AF: 0.134 Hom.: 206

Bravo AF: 0.139

Asia WGS AF: 0.139 AC: 484 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.2
DANN	Benign	0.76
PhyloP100		-1.2
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: rs3777312; hg19: chr5-9301496;