3-50173812-C-T

Variant names:

• chr3-50173812-C-T
• rs756077250
• ENST00000413852.5:c.-73C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001318798.2(SEMA3F):​c.-73C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,613,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: SEMA3F NM_001318798.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -5.58
• 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]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-50173812-C-T is Benign according to our data. Variant chr3-50173812-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3055104.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318798.2. 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
	SEMA3F	NM_004186.5	MANE Select	c.132C>T	p.Thr44Thr	synonymous	Exon 3 of 19	NP_004177.3
	SEMA3F	NM_001318798.2		c.-73C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 18	NP_001305727.1	C9JPG5
	SEMA3F	NM_001318800.2		c.132C>T	p.Thr44Thr	synonymous	Exon 3 of 18	NP_001305729.1	Q13275-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3F	ENST00000413852.5	TSL:1	c.-73C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 18	ENSP00000388931.1	C9JPG5
	SEMA3F	ENST00000002829.8	TSL:1 MANE Select	c.132C>T	p.Thr44Thr	synonymous	Exon 3 of 19	ENSP00000002829.3	Q13275-1
	SEMA3F	ENST00000434342.5	TSL:1	c.132C>T	p.Thr44Thr	synonymous	Exon 3 of 18	ENSP00000409859.1	Q13275-2

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152120 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.0000441

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000135 AC: 34 AN: 251132 AF XY: 0.000118

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000383 AC: 56 AN: 1461816 Hom.: 0 Cov.: 32 AF XY: 0.0000358 AC XY: 26 AN XY: 727200

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.000805 AC: 36 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1112006

Other (OTH) AF: 0.0000497 AC: 3 AN: 60390

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152120 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74294

African (AFR) AF: 0.0000242 AC: 1 AN: 41406

American (AMR) AF: 0.000131 AC: 2 AN: 15280

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68024

Other (OTH) AF: 0.000957 AC: 2 AN: 2090

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000718

ClinVar

ClinVar submissions as Germline

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	-0.85
CADD	Benign	0.19
DANN	Benign	0.73
PhyloP100		-5.6
PromoterAI		-0.35	Neutral

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: rs756077250; hg19: chr3-50211245;