NM_003966.3:c.225-1249G>C

Variant names:

• chr5-9319666-C-G
• rs3777325
• NM_003966.3:c.225-1249G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003966.3(SEMA5A):​c.225-1249G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 151,940 control chromosomes in the GnomAD database, including 2,352 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 0.16 (2352 hom., cov: 31)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.688
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA5A	NM_003966.3	c.225-1249G>C		intron_variant	Intron 4 of 22	ENST00000382496.10	NP_003957.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA5A	ENST00000382496.10	c.225-1249G>C		intron_variant	Intron 4 of 22	1	NM_003966.3	ENSP00000371936.5
SEMA5A	ENST00000652226.1	c.225-1249G>C		intron_variant	Intron 6 of 24			ENSP00000499013.1
SEMA5A	ENST00000513968.4	c.225-1249G>C		intron_variant	Intron 3 of 7	5		ENSP00000421961.1
SEMA5A	ENST00000509486.2	n.302-1249G>C		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24851 AN: 151824 Hom.: 2335 Cov.: 31

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0792

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.164 AC: 24921 AN: 151940 Hom.: 2352 Cov.: 31 AF XY: 0.163 AC XY: 12119 AN XY: 74254

African (AFR) AF: 0.252 AC: 10421 AN: 41408

American (AMR) AF: 0.146 AC: 2233 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 437 AN: 3472

East Asian (EAS) AF: 0.0797 AC: 411 AN: 5154

South Asian (SAS) AF: 0.194 AC: 932 AN: 4810

European-Finnish (FIN) AF: 0.117 AC: 1229 AN: 10542

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8664 AN: 67962

Other (OTH) AF: 0.176 AC: 372 AN: 2110

Alfa AF: 0.150 Hom.: 235

Bravo AF: 0.167

Asia WGS AF: 0.152 AC: 527 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.50
DANN	Benign	0.41
PhyloP100		-0.69
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: rs3777325; hg19: chr5-9319778;