NM_001358351.3:c.*1810A>G

Variant names:

• chr15-47773595-A-G
• rs3743286
• NM_001358351.3:c.*1810A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001358351.3(SEMA6D):​c.*1810A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,286 control chromosomes in the GnomAD database, including 3,935 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 0.21 (3927 hom., cov: 32)
  • Exomes 𝑓: 0.39 (8 hom.)
• Consequence: SEMA6D NM_001358351.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194

Genes affected

SEMA6D (HGNC:16770): (semaphorin 6D) Semaphorins are a large family, including both secreted and membrane associated proteins, many of which have been implicated as inhibitors or chemorepellents in axon pathfinding, fasciculation and branching, and target selection. All semaphorins possess a semaphorin (Sema) domain and a PSI domain (found in plexins, semaphorins and integrins) in the N-terminal extracellular portion. Additional sequence motifs C-terminal to the semaphorin domain allow classification into distinct subfamilies. Results demonstrate that transmembrane semaphorins, like the secreted ones, can act as repulsive axon guidance cues. This gene encodes a class 6 vertebrate transmembrane semaphorin that demonstrates alternative splicing. Several transcript variants have been identified and expression of the distinct encoded isoforms is thought to be regulated in a tissue- and development-dependent manner. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6D	NM_001358351.3	c.*1810A>G		3_prime_UTR_variant	Exon 19 of 19	ENST00000536845.7	NP_001345280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA6D	ENST00000536845.7	c.*1810A>G		3_prime_UTR_variant	Exon 19 of 19	2	NM_001358351.3	ENSP00000446152.3

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31727 AN: 152046 Hom.: 3926 Cov.: 32

Gnomad AFR AF: 0.0717

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.227

GnomAD4 exome AF: 0.385 AC: 47 AN: 122 Hom.: 8 Cov.: 0 AF XY: 0.354 AC XY: 29 AN XY: 82

Gnomad4 FIN exome AF: 0.392

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.209 AC: 31735 AN: 152164 Hom.: 3927 Cov.: 32 AF XY: 0.214 AC XY: 15891 AN XY: 74384

Gnomad4 AFR AF: 0.0716

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.226

Alfa AF: 0.241 Hom.: 5389

Bravo AF: 0.195

Asia WGS AF: 0.221 AC: 769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.2
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3743286; hg19: chr15-48065792;