NM_003966.3:c.-174-49222A>G

Variant names:

• chr5-9487074-T-C
• rs268519
• NM_003966.3:c.-174-49222A>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.-174-49222A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.967 in 152,072 control chromosomes in the GnomAD database, including 71,384 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 (71384 hom., cov: 30)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.889
• 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=-1.01).
• 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.-174-49222A>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.-174-49222A>G		intron_variant	Intron 1 of 22	1	NM_003966.3	ENSP00000371936.5
SEMA5A	ENST00000652226.1	c.-392-49222A>G		intron_variant	Intron 1 of 24			ENSP00000499013.1

Frequencies

GnomAD3 genomes AF: 0.967 AC: 146991 AN: 151956 Hom.: 71332 Cov.: 30

Gnomad AFR AF: 0.963

Gnomad AMI AF: 0.970

Gnomad AMR AF: 0.952

Gnomad ASJ AF: 0.986

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.995

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.994

Gnomad OTH AF: 0.968

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

GnomAD4 genome AF: 0.967 AC: 147099 AN: 152072 Hom.: 71384 Cov.: 30 AF XY: 0.963 AC XY: 71591 AN XY: 74322

African (AFR) AF: 0.963 AC: 39955 AN: 41478

American (AMR) AF: 0.952 AC: 14524 AN: 15264

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

East Asian (EAS) AF: 0.706 AC: 3627 AN: 5140

South Asian (SAS) AF: 0.877 AC: 4217 AN: 4810

European-Finnish (FIN) AF: 0.995 AC: 10536 AN: 10588

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

European-Non Finnish (NFE) AF: 0.994 AC: 67606 AN: 68004

Other (OTH) AF: 0.968 AC: 2043 AN: 2110

Alfa AF: 0.983 Hom.: 8941

Bravo AF: 0.963

Asia WGS AF: 0.845 AC: 2934 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.22
DANN	Benign	0.48
PhyloP100		-0.89
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: rs268519; hg19: chr5-9487186;