rs950179623

Variant names:

• chr3-50269311-C-A
• rs950179623
• NM_001290060.2:c.71C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-50269311-C-A
• chr3-50269311-C-T

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.71C>A​(p.Ala24Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000145 in 1,375,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A24V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: SEMA3B NM_001290060.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.45
• 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=0.16276765).

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.71C>A	p.Ala24Asp	missense	Exon 1 of 17	NP_001276989.1	Q13214-1
	SEMA3B	NM_001290061.1		c.71C>A	p.Ala24Asp	missense	Exon 1 of 17	NP_001276990.1	Q13214
	SEMA3B	NM_001435956.1		c.71C>A	p.Ala24Asp	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.71C>A	p.Ala24Asp	missense	Exon 1 of 17	ENSP00000484146.1	Q13214-1
	SEMA3B	ENST00000611067.4	TSL:1	c.71C>A	p.Ala24Asp	missense	Exon 1 of 17	ENSP00000480680.1	A0A0C4DGV8
	SEMA3B	ENST00000433753.4	TSL:1	c.71C>A	p.Ala24Asp	missense	Exon 1 of 17	ENSP00000485281.1	Q13214-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1375676 Hom.: 0 Cov.: 31 AF XY: 0.00000147 AC XY: 1 AN XY: 678868

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30674

American (AMR) AF: 0.00 AC: 0 AN: 31602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24314

East Asian (EAS) AF: 0.00 AC: 0 AN: 35622

South Asian (SAS) AF: 0.00 AC: 0 AN: 77918

European-Finnish (FIN) AF: 0.0000256 AC: 1 AN: 39076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5300

European-Non Finnish (NFE) AF: 9.31e-7 AC: 1 AN: 1074012

Other (OTH) AF: 0.00 AC: 0 AN: 57158

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	19
DANN	Benign	0.72
DEOGEN2	Benign	0.099	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.62	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.99	T
PhyloP100		4.5
PrimateAI	Uncertain	0.65	T
Sift4G	Benign	0.38	T
Polyphen		0.13	B
Vest4		0.41
MutPred		0.23		Loss of glycosylation at P26 (P = 0.0631)
MVP		0.18
ClinPred		0.91	D
GERP RS		4.1
PromoterAI		-0.024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.12
gMVP		0.54
Mutation Taster		=100/0	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: rs950179623; hg19: chr3-50306743;