NM_003966.3:c.-174-49984A>G

Variant names:

• chr5-9487836-T-C
• rs268521
• NM_003966.3:c.-174-49984A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003966.3(SEMA5A):​c.-174-49984A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.968 in 152,202 control chromosomes in the GnomAD database, including 71,605 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.97 (71605 hom., cov: 32)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 1 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA5A	NM_003966.3	c.-174-49984A>G		intron_variant	Intron 1 of 22	ENST00000382496.10	NP_003957.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA5A	ENST00000382496.10	c.-174-49984A>G		intron_variant	Intron 1 of 22	1	NM_003966.3	ENSP00000371936.5
SEMA5A	ENST00000652226.1	c.-392-49984A>G		intron_variant	Intron 1 of 24			ENSP00000499013.1

Frequencies

GnomAD3 genomes AF: 0.968 AC: 147274 AN: 152084 Hom.: 71551 Cov.: 32

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.970

Gnomad AMR AF: 0.952

Gnomad ASJ AF: 0.986

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.995

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.994

Gnomad OTH AF: 0.971

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.968 AC: 147385 AN: 152202 Hom.: 71605 Cov.: 32 AF XY: 0.964 AC XY: 71736 AN XY: 74394

African (AFR) AF: 0.967 AC: 40167 AN: 41532

American (AMR) AF: 0.952 AC: 14534 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.986 AC: 3424 AN: 3472

East Asian (EAS) AF: 0.704 AC: 3627 AN: 5150

South Asian (SAS) AF: 0.877 AC: 4227 AN: 4822

European-Finnish (FIN) AF: 0.995 AC: 10563 AN: 10616

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.994 AC: 67630 AN: 68030

Other (OTH) AF: 0.971 AC: 2046 AN: 2108

Alfa AF: 0.978 Hom.: 6745

Bravo AF: 0.965

Asia WGS AF: 0.845 AC: 2938 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.56
DANN	Benign	0.48
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs268521; hg19: chr5-9487948;