5-9298005-A-C

Variant names:

• chr5-9298005-A-C
• rs17196572
• NM_003966.3:c.270+20367T>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.270+20367T>G 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 1,603 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 (1603 hom., cov: 32)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• 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 (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+20367T>G		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+20367T>G		intron_variant	Intron 5 of 22	1	NM_003966.3	ENSP00000371936.5
SEMA5A	ENST00000652226.1	c.270+20367T>G		intron_variant	Intron 7 of 24			ENSP00000499013.1
SEMA5A	ENST00000513968.4	c.270+20367T>G		intron_variant	Intron 4 of 7	5		ENSP00000421961.1
SEMA5A	ENST00000509486.2	n.348-17198T>G		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21295 AN: 152034 Hom.: 1598 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0781

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.127

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: 21330 AN: 152152 Hom.: 1603 Cov.: 32 AF XY: 0.141 AC XY: 10490 AN XY: 74386

African (AFR) AF: 0.169 AC: 7011 AN: 41474

American (AMR) AF: 0.136 AC: 2087 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 435 AN: 3466

East Asian (EAS) AF: 0.0785 AC: 406 AN: 5172

South Asian (SAS) AF: 0.194 AC: 934 AN: 4822

European-Finnish (FIN) AF: 0.117 AC: 1240 AN: 10604

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8602 AN: 68000

Other (OTH) AF: 0.155 AC: 328 AN: 2112

Alfa AF: 0.137 Hom.: 256

Bravo AF: 0.140

Asia WGS AF: 0.140 AC: 486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.66
PhyloP100		0.25
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: rs17196572; hg19: chr5-9298117;