Genetic Variant SEMA3D:c.861+62_861+71delATATATATAT (chr7-85055645-CATATATATAT-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001384900.1(SEMA3D):c.861+62_861+71delATATATATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 159,726 control chromosomes in the GnomAD database, including 112 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.027 ( 108 hom., cov: 0)

Exomes 𝑓: 0.012 ( 4 hom. )

Consequence

SEMA3D
NM_001384900.1 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.718

Publications

1 publications found

Variant links:

Genes affected

SEMA3D (HGNC:10726): (semaphorin 3D) 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 like domain and a C-terminal basic domain. The protein encoded by this gene binds neuropilin and plays an important role in cardiovascular development. [provided by RefSeq, Aug 2016]

SEMA3D Gene-Disease associations (from GenCC):

skeletal dysplasia
Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

SEMA3D links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0762 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384900.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SEMA3D	NM_001384900.1	MANE Select	c.861+62_861+71delATATATATAT	intron	N/A	NP_001371829.1	O95025
SEMA3D	NM_001384901.1		c.861+62_861+71delATATATATAT	intron	N/A	NP_001371830.1	O95025
SEMA3D	NM_001384902.1		c.861+62_861+71delATATATATAT	intron	N/A	NP_001371831.1	O95025

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SEMA3D	ENST00000284136.11	TSL:5 MANE Select	c.861+62_861+71delATATATATAT	intron	N/A	ENSP00000284136.6	O95025
SEMA3D	ENST00000444867.1	TSL:1	c.861+62_861+71delATATATATAT	intron	N/A	ENSP00000401366.1	C9JYT6
SEMA3D	ENST00000916323.1		c.861+62_861+71delATATATATAT	intron	N/A	ENSP00000586382.1

Frequencies

GnomAD3 genomes

AF:

0.0266

AC:

2975

AN:

111644

Hom.:

107

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0787

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0137

Gnomad ASJ

AF:

0.00577

Gnomad EAS

AF:

0.00663

Gnomad SAS

AF:

0.0196

Gnomad FIN

AF:

0.00137

Gnomad MID

AF:

0.0144

Gnomad NFE

AF:

0.00564

Gnomad OTH

AF:

0.0213

GnomAD4 exome

AF:

0.0116

AC:

556

AN:

48080

Hom.:

AF XY:

0.0120

AC XY:

334

AN XY:

27766

show subpopulations

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

African (AFR)

AF:

0.0723

AC:

AN:

678

American (AMR)

AF:

0.0155

AC:

AN:

772

Ashkenazi Jewish (ASJ)

AF:

0.0113

AC:

AN:

706

East Asian (EAS)

AF:

0.0183

AC:

AN:

1036

South Asian (SAS)

AF:

0.0146

AC:

AN:

1024

European-Finnish (FIN)

AF:

0.0151

AC:

AN:

1260

Middle Eastern (MID)

AF:

0.00847

AC:

AN:

118

European-Non Finnish (NFE)

AF:

0.00987

AC:

401

AN:

40634

Other (OTH)

AF:

0.0173

AC:

AN:

1852

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.363

Heterozygous variant carriers

105

140

175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0267

AC:

2981

AN:

111646

Hom.:

108

Cov.:

AF XY:

0.0265

AC XY:

1373

AN XY:

51822

show subpopulations

African (AFR)

AF:

0.0789

AC:

2396

AN:

30386

American (AMR)

AF:

0.0137

AC:

131

AN:

9570

Ashkenazi Jewish (ASJ)

AF:

0.00577

AC:

AN:

2948

East Asian (EAS)

AF:

0.00667

AC:

AN:

3598

South Asian (SAS)

AF:

0.0194

AC:

AN:

2994

European-Finnish (FIN)

AF:

0.00137

AC:

AN:

3644

Middle Eastern (MID)

AF:

0.0150

AC:

AN:

200

European-Non Finnish (NFE)

AF:

0.00564

AC:

316

AN:

56062

Other (OTH)

AF:

0.0211

AC:

AN:

1466

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

Heterozygous variant carriers

108

217

325

434

542

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

173

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.72

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over