Variant 5-9050465-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003966.3(SEMA5A):c.2846-8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00517 in 1,611,948 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0052 ( 28 hom. )

Consequence

SEMA5A
NM_003966.3 splice_region, intron

Scores

Splicing: ADA: 0.00008183

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.75

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 5-9050465-A-G is Benign according to our data. Variant chr5-9050465-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 777593.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA5A	NM_003966.3 link	c.2846-8T>C		splice_region_variant, intron_variant		ENST00000382496.10	NP_003957.2	Q13591X5DR95

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA5A	ENST00000382496.10 link	c.2846-8T>C		splice_region_variant, intron_variant		1	NM_003966.3	ENSP00000371936.5		Q13591
SEMA5A	ENST00000652226.1 link	c.2846-8T>C		splice_region_variant, intron_variant				ENSP00000499013.1		Q13591

Frequencies

GnomAD3 genomes

AF:

0.00464

AC:

706

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.0362

Gnomad AMR

AF:

0.00706

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00169

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00647

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00424

AC:

1056

AN:

249284

Hom.:

AF XY:

0.00442

AC XY:

596

AN XY:

134732

show subpopulations

Gnomad AFR exome

AF:

0.000493

Gnomad AMR exome

AF:

0.00313

Gnomad ASJ exome

AF:

0.00818

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00167

Gnomad FIN exome

AF:

0.00166

Gnomad NFE exome

AF:

0.00654

Gnomad OTH exome

AF:

0.00563

GnomAD4 exome

AF:

0.00523

AC:

7630

AN:

1459608

Hom.:

Cov.:

AF XY:

0.00526

AC XY:

3819

AN XY:

725998

show subpopulations

Gnomad4 AFR exome

AF:

0.000808

Gnomad4 AMR exome

AF:

0.00333

Gnomad4 ASJ exome

AF:

0.00774

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00192

Gnomad4 FIN exome

AF:

0.00197

Gnomad4 NFE exome

AF:

0.00596

Gnomad4 OTH exome

AF:

0.00507

GnomAD4 genome

AF:

0.00463

AC:

706

AN:

152340

Hom.:

Cov.:

AF XY:

0.00474

AC XY:

353

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00705

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00169

Gnomad4 NFE

AF:

0.00647

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00504

Hom.:

Bravo

AF:

0.00470

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	SEMA5A: BP4, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

6.3

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000082

dbscSNV1_RF

Benign

0.014

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over