chr3-50159634-C-T

Variant names:

• chr3-50159634-C-T
• rs201364829
• NM_004186.5:c.12C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_004186.5(SEMA3F):​c.12C>T​(p.Ala4Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00015 in 1,609,210 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00030 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: SEMA3F NM_004186.5 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.02
• Publications: 0 publications found

Genes affected

SEMA3F (HGNC:10728): (semaphorin 3F) This gene encodes a member of the semaphorin III family of secreted signaling proteins that are involved in axon guidance during neuronal development. The encoded protein contains an N-terminal Sema domain, an immunoglobulin loop and a C-terminal basic domain. This gene is expressed by the endothelial cells where it was found to act in an autocrine fashion to induce apoptosis, inhibit cell proliferation and survival, and function as an anti-tumorigenic agent. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

SEMA3F Gene-Disease associations (from GenCC):

• hypogonadotropic hypogonadism

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 3-50159634-C-T is Benign according to our data. Variant chr3-50159634-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3051108.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.02 with no splicing effect.
• BS2: High AC in GnomAd4 at 46 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004186.5. 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
	SEMA3F	NM_004186.5	MANE Select	c.12C>T	p.Ala4Ala	synonymous	Exon 2 of 19	NP_004177.3
	SEMA3F	NM_001318800.2		c.12C>T	p.Ala4Ala	synonymous	Exon 2 of 18	NP_001305729.1	Q13275-2
	SEMA3F	NM_001318798.2		c.-135-58C>T		intron	N/A	NP_001305727.1	C9JPG5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3F	ENST00000002829.8	TSL:1 MANE Select	c.12C>T	p.Ala4Ala	synonymous	Exon 2 of 19	ENSP00000002829.3	Q13275-1
	SEMA3F	ENST00000434342.5	TSL:1	c.12C>T	p.Ala4Ala	synonymous	Exon 2 of 18	ENSP00000409859.1	Q13275-2
	SEMA3F	ENST00000413852.5	TSL:1	c.-135-58C>T		intron	N/A	ENSP00000388931.1	C9JPG5

Frequencies

GnomAD3 genomes AF: 0.000302 AC: 46 AN: 152204 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000141 AC: 35 AN: 247524 AF XY: 0.000164

Gnomad AFR exome AF: 0.0000624

Gnomad AMR exome AF: 0.000210

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000133

Gnomad OTH exome AF: 0.000332

GnomAD4 exome AF: 0.000135 AC: 196 AN: 1456888 Hom.: 0 Cov.: 28 AF XY: 0.000139 AC XY: 101 AN XY: 724920

African (AFR) AF: 0.0000600 AC: 2 AN: 33314

American (AMR) AF: 0.000477 AC: 21 AN: 43988

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26062

East Asian (EAS) AF: 0.000102 AC: 4 AN: 39232

South Asian (SAS) AF: 0.000268 AC: 23 AN: 85800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53146

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.000119 AC: 132 AN: 1109396

Other (OTH) AF: 0.000233 AC: 14 AN: 60196

GnomAD4 genome AF: 0.000302 AC: 46 AN: 152322 Hom.: 1 Cov.: 33 AF XY: 0.000309 AC XY: 23 AN XY: 74492

African (AFR) AF: 0.0000481 AC: 2 AN: 41562

American (AMR) AF: 0.00235 AC: 36 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68032

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.000567

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SEMA3F-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	8.4
DANN	Benign	0.76
PhyloP100		1.0
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: rs201364829; hg19: chr3-50197067;