Genetic Variant SEMA3D:c.861+48_861+71delATATATATATATATATATATATAT (chr7-85055645-CATATATATATATATATATATATAT-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001384900.1(SEMA3D):c.861+48_861+71delATATATATATATATATATATATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000263 in 159,806 control chromosomes in the GnomAD database, including 2 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00062 ( 2 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: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

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+48_861+71delATATATATATATATATATATATAT	intron	N/A	NP_001371829.1	O95025
SEMA3D	NM_001384901.1		c.861+48_861+71delATATATATATATATATATATATAT	intron	N/A	NP_001371830.1	O95025
SEMA3D	NM_001384902.1		c.861+48_861+71delATATATATATATATATATATATAT	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+48_861+71delATATATATATATATATATATATAT	intron	N/A	ENSP00000284136.6	O95025
SEMA3D	ENST00000444867.1	TSL:1	c.861+48_861+71delATATATATATATATATATATATAT	intron	N/A	ENSP00000401366.1	C9JYT6
SEMA3D	ENST00000916323.1		c.861+48_861+71delATATATATATATATATATATATAT	intron	N/A	ENSP00000586382.1

Frequencies

GnomAD3 genomes

AF:

0.000107

AC:

AN:

111640

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000659

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000313

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000333

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000107

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000623

AC:

AN:

48164

Hom.:

AF XY:

0.000467

AC XY:

AN XY:

27810

show subpopulations

African (AFR)

AF:

0.00145

AC:

AN:

690

American (AMR)

AF:

0.00

AC:

AN:

774

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

712

East Asian (EAS)

AF:

0.00578

AC:

AN:

1038

South Asian (SAS)

AF:

0.000978

AC:

AN:

1022

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1262

Middle Eastern (MID)

AF:

0.00

AC:

AN:

118

European-Non Finnish (NFE)

AF:

0.000492

AC:

AN:

40688

Other (OTH)

AF:

0.00108

AC:

AN:

1860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

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:

0.000107

AC:

AN:

111642

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

51824

show subpopulations

African (AFR)

AF:

0.0000658

AC:

AN:

30380

American (AMR)

AF:

0.000313

AC:

AN:

9572

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2948

East Asian (EAS)

AF:

0.00

AC:

AN:

3598

South Asian (SAS)

AF:

0.000334

AC:

AN:

2992

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3644

Middle Eastern (MID)

AF:

0.00

AC:

AN:

200

European-Non Finnish (NFE)

AF:

0.000107

AC:

AN:

56062

Other (OTH)

AF:

0.00

AC:

AN:

1468

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.658

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

0.72

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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7-85055645-CATATATATATATATATATATATATATATAT-CATATAT

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