rs3777311

Variant names:

• chr5-9301212-G-T
• rs3777311
• NM_003966.3:c.270+17160C>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+17160C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,226 control chromosomes in the GnomAD database, including 1,572 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 (1572 hom., cov: 33)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267
• 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=-0.68).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.183 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.270+17160C>A		intron	N/A	NP_003957.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA5A	ENST00000382496.10	TSL:1 MANE Select	c.270+17160C>A		intron	N/A	ENSP00000371936.5
	SEMA5A	ENST00000652226.1		c.270+17160C>A		intron	N/A	ENSP00000499013.1
	SEMA5A	ENST00000897596.1		c.270+17160C>A		intron	N/A	ENSP00000567655.1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21183 AN: 152108 Hom.: 1567 Cov.: 33

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0793

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.139 AC: 21217 AN: 152226 Hom.: 1572 Cov.: 33 AF XY: 0.140 AC XY: 10436 AN XY: 74430

African (AFR) AF: 0.168 AC: 6987 AN: 41524

American (AMR) AF: 0.137 AC: 2088 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 435 AN: 3468

East Asian (EAS) AF: 0.0797 AC: 413 AN: 5182

South Asian (SAS) AF: 0.193 AC: 930 AN: 4822

European-Finnish (FIN) AF: 0.117 AC: 1236 AN: 10600

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

European-Non Finnish (NFE) AF: 0.126 AC: 8583 AN: 68020

Other (OTH) AF: 0.154 AC: 326 AN: 2112

Alfa AF: 0.135 Hom.: 522

Bravo AF: 0.139

Asia WGS AF: 0.139 AC: 485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.4
DANN	Benign	0.82
PhyloP100		0.27
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: rs3777311; hg19: chr5-9301324;