rs10234961

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006080.3(SEMA3A):c.1361-28G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0154 in 1,302,130 control chromosomes in the GnomAD database, including 472 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 221 hom., cov: 33)

Exomes 𝑓: 0.013 ( 251 hom. )

Consequence

SEMA3A
NM_006080.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.325

Publications

2 publications found

Variant links:

Genes affected

SEMA3A (HGNC:10723): (semaphorin 3A) This gene is a member of the semaphorin family and encodes a protein with an Ig-like C2-type (immunoglobulin-like) domain, a PSI domain and a Sema domain. This secreted protein can function as either a chemorepulsive agent, inhibiting axonal outgrowth, or as a chemoattractive agent, stimulating the growth of apical dendrites. In both cases, the protein is vital for normal neuronal pattern development. Increased expression of this protein is associated with schizophrenia and is seen in a variety of human tumor cell lines. Also, aberrant release of this protein is associated with the progression of Alzheimer's disease. [provided by RefSeq, Jul 2008]

SEMA3A Gene-Disease associations (from GenCC):

skeletal dysplasia
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
hypogonadotropic hypogonadism 16 with or without anosmia
Inheritance: AD, SD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
multiple congenital anomalies/dysmorphic syndrome
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
Brugada syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Kallmann syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SEMA3A links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_006080.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 7-84002074-C-G is Benign according to our data. Variant chr7-84002074-C-G is described in ClinVar as Benign. ClinVar VariationId is 1183281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0966 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006080.3. 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
	SEMA3A	NM_006080.3	MANE Select	c.1361-28G>C		intron	N/A	NP_006071.1	Q14563

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SEMA3A	ENST00000265362.9	TSL:1 MANE Select	c.1361-28G>C	intron	N/A	ENSP00000265362.3	Q14563
SEMA3A	ENST00000436949.5	TSL:5	c.1361-28G>C	intron	N/A	ENSP00000415260.1	Q14563
SEMA3A	ENST00000864988.1		c.1361-28G>C	intron	N/A	ENSP00000535047.1

Frequencies

GnomAD3 genomes

AF:

0.0348

AC:

5295

AN:

152060

Hom.:

220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0990

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.0143

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.0183

Gnomad SAS

AF:

0.0211

Gnomad FIN

AF:

0.00189

Gnomad MID

AF:

0.0510

Gnomad NFE

AF:

0.00943

Gnomad OTH

AF:

0.0311

GnomAD2 exomes

AF:

0.0171

AC:

4095

AN:

239940

AF XY:

0.0167

show subpopulations

Gnomad AFR exome

AF:

0.0991

Gnomad AMR exome

AF:

0.0106

Gnomad ASJ exome

AF:

0.0145

Gnomad EAS exome

AF:

0.0171

Gnomad FIN exome

AF:

0.00123

Gnomad NFE exome

AF:

0.00958

Gnomad OTH exome

AF:

0.0151

GnomAD4 exome

AF:

0.0128

AC:

14696

AN:

1149950

Hom.:

251

Cov.:

AF XY:

0.0129

AC XY:

7561

AN XY:

587198

show subpopulations

African (AFR)

AF:

0.102

AC:

2750

AN:

27078

American (AMR)

AF:

0.0113

AC:

476

AN:

42226

Ashkenazi Jewish (ASJ)

AF:

0.0131

AC:

311

AN:

23682

East Asian (EAS)

AF:

0.0138

AC:

520

AN:

37766

South Asian (SAS)

AF:

0.0210

AC:

1651

AN:

78678

European-Finnish (FIN)

AF:

0.00153

AC:

AN:

52840

Middle Eastern (MID)

AF:

0.0573

AC:

296

AN:

5168

European-Non Finnish (NFE)

AF:

0.00919

AC:

7650

AN:

832630

Other (OTH)

AF:

0.0193

AC:

961

AN:

49882

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

683

1366

2050

2733

3416

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

312

624

936

1248

1560

<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:

0.0349

AC:

5312

AN:

152180

Hom.:

221

Cov.:

AF XY:

0.0337

AC XY:

2507

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.0991

AC:

4114

AN:

41512

American (AMR)

AF:

0.0143

AC:

219

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0101

AC:

AN:

3468

East Asian (EAS)

AF:

0.0188

AC:

AN:

5168

South Asian (SAS)

AF:

0.0209

AC:

101

AN:

4830

European-Finnish (FIN)

AF:

0.00189

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00943

AC:

641

AN:

68000

Other (OTH)

AF:

0.0307

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

252

505

757

1010

1262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0229

Hom.:

Bravo

AF:

0.0381

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.0

(source)

DANN

Benign

0.62

PhyloP100

-0.33

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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