NM_003966.3:c.225-4938C>T

Variant names:

• chr5-9323355-G-A
• rs3777327
• NM_003966.3:c.225-4938C>T

Variant summary

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

The NM_003966.3(SEMA5A):​c.225-4938C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,044 control chromosomes in the GnomAD database, including 1,501 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 (1501 hom., cov: 32)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.181 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.225-4938C>T		intron	N/A	NP_003957.2	X5DR95

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA5A	ENST00000382496.10	TSL:1 MANE Select	c.225-4938C>T		intron	N/A	ENSP00000371936.5	Q13591
	SEMA5A	ENST00000652226.1		c.225-4938C>T		intron	N/A	ENSP00000499013.1	Q13591
	SEMA5A	ENST00000897596.1		c.225-4938C>T		intron	N/A	ENSP00000567655.1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20803 AN: 151926 Hom.: 1499 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0787

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.156

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: 0.137 AC: 20827 AN: 152044 Hom.: 1501 Cov.: 32 AF XY: 0.138 AC XY: 10222 AN XY: 74328

African (AFR) AF: 0.159 AC: 6611 AN: 41466

American (AMR) AF: 0.137 AC: 2086 AN: 15276

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

East Asian (EAS) AF: 0.0793 AC: 410 AN: 5172

South Asian (SAS) AF: 0.191 AC: 920 AN: 4820

European-Finnish (FIN) AF: 0.117 AC: 1234 AN: 10548

Middle Eastern (MID) AF: 0.164 AC: 48 AN: 292

European-Non Finnish (NFE) AF: 0.126 AC: 8589 AN: 67978

Other (OTH) AF: 0.154 AC: 325 AN: 2112

Alfa AF: 0.135 Hom.: 183

Bravo AF: 0.136

Asia WGS AF: 0.139 AC: 479 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.33
DANN	Benign	0.32
PhyloP100		-1.1
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: rs3777327; hg19: chr5-9323467;