7-85055645-CATATATATATATATATATATATATATATAT-CATATATATATATATATATATATAT

Variant names:

• chr7-85055645-CATATAT-C
• rs56131427
• NM_001384900.1:c.861+66_861+71delATATAT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001384900.1(SEMA3D):​c.861+66_861+71delATATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0819 in 159,134 control chromosomes in the GnomAD database, including 535 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.10 (531 hom., cov: 0)
  • Exomes 𝑓: 0.032 (4 hom.)
• Consequence: SEMA3D NM_001384900.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170
• Publications: 1 publications found

Genes affected

SEMA3D (HGNC:10726): (semaphorin 3D) This gene encodes a member of the semaphorin III family of secreted signaling proteins that are involved in axon guidance during neuronal development. The encoded protein contains an N-terminal Sema domain, an immunoglobulin like domain and a C-terminal basic domain. The protein encoded by this gene binds neuropilin and plays an important role in cardiovascular development. [provided by RefSeq, Aug 2016]

SEMA3D Gene-Disease associations (from GenCC):

• skeletal dysplasia

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384900.1. 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
	SEMA3D	NM_001384900.1	MANE Select	c.861+66_861+71delATATAT		intron	N/A	NP_001371829.1	O95025
	SEMA3D	NM_001384901.1		c.861+66_861+71delATATAT		intron	N/A	NP_001371830.1	O95025
	SEMA3D	NM_001384902.1		c.861+66_861+71delATATAT		intron	N/A	NP_001371831.1	O95025

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3D	ENST00000284136.11	TSL:5 MANE Select	c.861+66_861+71delATATAT		intron	N/A	ENSP00000284136.6	O95025
	SEMA3D	ENST00000444867.1	TSL:1	c.861+66_861+71delATATAT		intron	N/A	ENSP00000401366.1	C9JYT6
	SEMA3D	ENST00000916323.1		c.861+66_861+71delATATAT		intron	N/A	ENSP00000586382.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 11495 AN: 111296 Hom.: 531 Cov.: 0

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.0527

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0617

Gnomad MID AF: 0.0777

Gnomad NFE AF: 0.0795

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.0323 AC: 1544 AN: 47838 Hom.: 4 AF XY: 0.0331 AC XY: 913 AN XY: 27594

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0452 AC: 31 AN: 686

American (AMR) AF: 0.0703 AC: 54 AN: 768

Ashkenazi Jewish (ASJ) AF: 0.0437 AC: 31 AN: 710

East Asian (EAS) AF: 0.0699 AC: 71 AN: 1016

South Asian (SAS) AF: 0.0530 AC: 54 AN: 1018

European-Finnish (FIN) AF: 0.0416 AC: 52 AN: 1250

Middle Eastern (MID) AF: 0.00862 AC: 1 AN: 116

European-Non Finnish (NFE) AF: 0.0291 AC: 1176 AN: 40430

Other (OTH) AF: 0.0401 AC: 74 AN: 1844

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.103 AC: 11496 AN: 111296 Hom.: 531 Cov.: 0 AF XY: 0.104 AC XY: 5382 AN XY: 51660

African (AFR) AF: 0.133 AC: 4021 AN: 30248

American (AMR) AF: 0.128 AC: 1217 AN: 9538

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 431 AN: 2946

East Asian (EAS) AF: 0.152 AC: 545 AN: 3580

South Asian (SAS) AF: 0.134 AC: 400 AN: 2984

European-Finnish (FIN) AF: 0.0617 AC: 224 AN: 3630

Middle Eastern (MID) AF: 0.0808 AC: 16 AN: 198

European-Non Finnish (NFE) AF: 0.0795 AC: 4444 AN: 55932

Other (OTH) AF: 0.107 AC: 157 AN: 1462

Alfa AF: 0.0671 Hom.: 173

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs56131427; hg19: chr7-84684961;