3-50159664-C-T

Variant names:

• chr3-50159664-C-T
• rs1046953
• NM_004186.5:c.42C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_004186.5(SEMA3F):​c.42C>T​(p.Thr14Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 1,610,692 control chromosomes in the GnomAD database, including 145,180 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.39 (11829 hom., cov: 33)
  • Exomes 𝑓: 0.42 (133351 hom.)
• Consequence: SEMA3F NM_004186.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.943
• Publications: 23 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 3-50159664-C-T is Benign according to our data. Variant chr3-50159664-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060562.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.943 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

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.42C>T	p.Thr14Thr	synonymous	Exon 2 of 19	NP_004177.3
	SEMA3F	NM_001318800.2		c.42C>T	p.Thr14Thr	synonymous	Exon 2 of 18	NP_001305729.1	Q13275-2
	SEMA3F	NM_001318798.2		c.-135-28C>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.42C>T	p.Thr14Thr	synonymous	Exon 2 of 19	ENSP00000002829.3	Q13275-1
	SEMA3F	ENST00000434342.5	TSL:1	c.42C>T	p.Thr14Thr	synonymous	Exon 2 of 18	ENSP00000409859.1	Q13275-2
	SEMA3F	ENST00000413852.5	TSL:1	c.-135-28C>T		intron	N/A	ENSP00000388931.1	C9JPG5

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58790 AN: 151982 Hom.: 11822 Cov.: 33

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.378

GnomAD2 exomes AF: 0.411 AC: 102445 AN: 249386 AF XY: 0.430

Gnomad AFR exome AF: 0.331

Gnomad AMR exome AF: 0.268

Gnomad ASJ exome AF: 0.412

Gnomad EAS exome AF: 0.184

Gnomad FIN exome AF: 0.454

Gnomad NFE exome AF: 0.423

Gnomad OTH exome AF: 0.407

GnomAD4 exome AF: 0.420 AC: 612973 AN: 1458590 Hom.: 133351 Cov.: 34 AF XY: 0.429 AC XY: 311006 AN XY: 725740

African (AFR) AF: 0.325 AC: 10849 AN: 33402

American (AMR) AF: 0.274 AC: 12187 AN: 44522

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 10875 AN: 26094

East Asian (EAS) AF: 0.230 AC: 9092 AN: 39558

South Asian (SAS) AF: 0.665 AC: 57213 AN: 86054

European-Finnish (FIN) AF: 0.448 AC: 23806 AN: 53092

Middle Eastern (MID) AF: 0.418 AC: 2409 AN: 5760

European-Non Finnish (NFE) AF: 0.417 AC: 462284 AN: 1109814

Other (OTH) AF: 0.402 AC: 24258 AN: 60294

GnomAD4 genome AF: 0.387 AC: 58820 AN: 152102 Hom.: 11829 Cov.: 33 AF XY: 0.391 AC XY: 29042 AN XY: 74354

African (AFR) AF: 0.329 AC: 13638 AN: 41484

American (AMR) AF: 0.304 AC: 4654 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1489 AN: 3470

East Asian (EAS) AF: 0.203 AC: 1051 AN: 5176

South Asian (SAS) AF: 0.663 AC: 3198 AN: 4822

European-Finnish (FIN) AF: 0.461 AC: 4878 AN: 10580

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28637 AN: 67960

Other (OTH) AF: 0.378 AC: 799 AN: 2112

Alfa AF: 0.402 Hom.: 5376

Bravo AF: 0.360

Asia WGS AF: 0.461 AC: 1606 AN: 3478

EpiCase AF: 0.426

EpiControl AF: 0.419

ClinVar

ClinVar submissions as Germline

Significance: 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	-0.46
CADD	Benign	8.3
DANN	Benign	0.78
PhyloP100		-0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1046953; hg19: chr3-50197097; COSMIC: COSV50029201; COSMIC: COSV50029201;