Genetic Variant SEMA3D:c.861+62_861+71dupATATATATAT (chr7-85055645-C-CATATATATAT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001384900.1(SEMA3D):c.861+62_861+71dupATATATATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000726 in 159,754 control chromosomes in the GnomAD database, including 1 homozygotes. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0010 ( 1 hom., cov: 0)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

SEMA3D
NM_001384900.1 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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+71dupATATATATAT	intron	N/A	NP_001371829.1	O95025
SEMA3D	NM_001384901.1		c.861+62_861+71dupATATATATAT	intron	N/A	NP_001371830.1	O95025
SEMA3D	NM_001384902.1		c.861+62_861+71dupATATATATAT	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+71_861+72insATATATATAT	intron	N/A	ENSP00000284136.6	O95025
SEMA3D	ENST00000444867.1	TSL:1	c.861+71_861+72insATATATATAT	intron	N/A	ENSP00000401366.1	C9JYT6
SEMA3D	ENST00000916323.1		c.861+71_861+72insATATATATAT	intron	N/A	ENSP00000586382.1

Frequencies

GnomAD3 genomes

AF:

0.00103

AC:

115

AN:

111586

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000626

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00199

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00249

Gnomad SAS

AF:

0.000333

Gnomad FIN

AF:

0.000274

Gnomad MID

AF:

0.00481

Gnomad NFE

AF:

0.00112

Gnomad OTH

AF:

0.00138

GnomAD4 exome

AF:

0.0000208

AC:

AN:

48164

Hom.:

AF XY:

0.00

AC XY:

AN XY:

27804

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

690

American (AMR)

AF:

0.00

AC:

AN:

774

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

712

East Asian (EAS)

AF:

0.00

AC:

AN:

1038

South Asian (SAS)

AF:

0.00

AC:

AN:

1024

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1262

Middle Eastern (MID)

AF:

0.00

AC:

AN:

118

European-Non Finnish (NFE)

AF:

0.0000246

AC:

AN:

40688

Other (OTH)

AF:

0.00

AC:

AN:

1858

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00103

AC:

115

AN:

111590

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

AN XY:

51794

show subpopulations

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

African (AFR)

AF:

0.000626

AC:

AN:

30374

American (AMR)

AF:

0.00199

AC:

AN:

9566

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2948

East Asian (EAS)

AF:

0.00250

AC:

AN:

3594

South Asian (SAS)

AF:

0.000335

AC:

AN:

2988

European-Finnish (FIN)

AF:

0.000274

AC:

AN:

3644

Middle Eastern (MID)

AF:

0.00500

AC:

AN:

200

European-Non Finnish (NFE)

AF:

0.00112

AC:

AN:

56032

Other (OTH)

AF:

0.00136

AC:

AN:

1466

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 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: 0.386

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.00

Hom.:

173

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0

Splicing

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

Publications

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7-85055645-CATATATATATATATATATATATATATATAT-CATATATATATATATATATATATATATATATATATATATAT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over