3-50269321-C-A

Variant names:

• chr3-50269321-C-A
• rs927353157
• NM_001290060.2:c.81C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001290060.2(SEMA3B):​c.81C>A​(p.Ser27Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S27T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SEMA3B NM_001290060.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550
• Publications: 0 publications found

Genes affected

SEMA3B (HGNC:10724): (semaphorin 3B) The protein encoded by this gene belongs to the class-3 semaphorin/collapsin family, whose members function in growth cone guidance during neuronal development. This family member inhibits axonal extension and has been shown to act as a tumor suppressor by inducing apoptosis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2014]

SEMA3B-AS1 (HGNC:49096): (SEMA3B antisense RNA 1 (head to head))

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13148373).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290060.2. 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
	SEMA3B	NM_001290060.2	MANE Select	c.81C>A	p.Ser27Arg	missense	Exon 1 of 17	NP_001276989.1	Q13214-1
	SEMA3B	NM_001290061.1		c.81C>A	p.Ser27Arg	missense	Exon 1 of 17	NP_001276990.1	Q13214
	SEMA3B	NM_001435956.1		c.81C>A	p.Ser27Arg	missense	Exon 4 of 20	NP_001422885.1	Q13214-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3B	ENST00000616701.5	TSL:1 MANE Select	c.81C>A	p.Ser27Arg	missense	Exon 1 of 17	ENSP00000484146.1	Q13214-1
	SEMA3B	ENST00000611067.4	TSL:1	c.81C>A	p.Ser27Arg	missense	Exon 1 of 17	ENSP00000480680.1	A0A0C4DGV8
	SEMA3B	ENST00000433753.4	TSL:1	c.81C>A	p.Ser27Arg	missense	Exon 1 of 17	ENSP00000485281.1	Q13214-2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152122 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1363540 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 672754

African (AFR) AF: 0.00 AC: 0 AN: 29808

American (AMR) AF: 0.00 AC: 0 AN: 27910

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23538

East Asian (EAS) AF: 0.00 AC: 0 AN: 35540

South Asian (SAS) AF: 0.00 AC: 0 AN: 76128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5216

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1069482

Other (OTH) AF: 0.00 AC: 0 AN: 56520

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152122 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74308

African (AFR) AF: 0.0000241 AC: 1 AN: 41424

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
CADD	Benign	16
DEOGEN2	Benign	0.085	T
LIST_S2	Benign	0.76	T
MetaRNN	Benign	0.13	T
PhyloP100		-0.055
Sift4G	Benign	0.30	T
Vest4		0.27
PromoterAI		0.049	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.031
gMVP		0.49
Mutation Taster		=99/1	polymorphism

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: rs927353157;