Genetic Variant SEMA5A:c.*2868G>C (chr5-9040029-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003966.3(SEMA5A):c.*2868G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 152,142 control chromosomes in the GnomAD database, including 38,593 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.70 ( 38592 hom., cov: 33)

Exomes 𝑓: 0.67 ( 1 hom. )

Consequence

SEMA5A
NM_003966.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0560

Publications

10 publications found

Variant links:

Genes affected

SEMA5A (HGNC:10736): (semaphorin 5A) This gene belongs to the semaphorin gene family that encodes membrane proteins containing a semaphorin domain and several thrombospondin type-1 repeats. Members of this family are involved in axonal guidance during neural development. This gene has been implicated as an autism susceptibility gene.[provided by RefSeq, Jan 2010]

SEMA5A Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia

SEMA5A links:

ENSG00000250619 (HGNC:):

ENSG00000250619 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003966.3. 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
	SEMA5A	NM_003966.3	MANE Select	c.*2868G>C		3_prime_UTR	Exon 23 of 23	NP_003957.2	X5DR95

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SEMA5A	ENST00000382496.10	TSL:1 MANE Select	c.*2868G>C	3_prime_UTR	Exon 23 of 23	ENSP00000371936.5	Q13591
SEMA5A	ENST00000897596.1		c.*2868G>C	3_prime_UTR	Exon 24 of 24	ENSP00000567655.1
SEMA5A	ENST00000897597.1		c.*2868G>C	3_prime_UTR	Exon 24 of 24	ENSP00000567656.1

Frequencies

GnomAD3 genomes

AF:

0.705

AC:

107140

AN:

152018

Hom.:

38583

Cov.:

show subpopulations

Gnomad AFR

AF:

0.550

Gnomad AMI

AF:

0.615

Gnomad AMR

AF:

0.788

Gnomad ASJ

AF:

0.701

Gnomad EAS

AF:

0.930

Gnomad SAS

AF:

0.774

Gnomad FIN

AF:

0.813

Gnomad MID

AF:

0.655

Gnomad NFE

AF:

0.743

Gnomad OTH

AF:

0.703

GnomAD4 exome

AF:

0.667

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.667

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.705

AC:

107198

AN:

152136

Hom.:

38592

Cov.:

AF XY:

0.712

AC XY:

52970

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.549

AC:

22788

AN:

41472

American (AMR)

AF:

0.788

AC:

12044

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.701

AC:

2434

AN:

3470

East Asian (EAS)

AF:

0.930

AC:

4812

AN:

5176

South Asian (SAS)

AF:

0.773

AC:

3728

AN:

4820

European-Finnish (FIN)

AF:

0.813

AC:

8610

AN:

10590

Middle Eastern (MID)

AF:

0.660

AC:

194

AN:

294

European-Non Finnish (NFE)

AF:

0.743

AC:

50545

AN:

68008

Other (OTH)

AF:

0.702

AC:

1483

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1583

3166

4748

6331

7914

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

830

1660

2490

3320

4150

<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:

0.717

Hom.:

4929

Bravo

AF:

0.694

Asia WGS

AF:

0.784

AC:

2725

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.74

(source)

DANN

Benign

0.42

PhyloP100

-0.056

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over