7-85055645-CATATATATATATATATATATATATATATAT-CATATATATATATATATATATAT

Variant names:

• chr7-85055645-CATATATAT-C
• rs56131427
• NM_001384900.1:c.861+64_861+71delATATATAT

Variant summary

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

The NM_001384900.1(SEMA3D):​c.861+64_861+71delATATATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0696 in 159,428 control chromosomes in the GnomAD database, including 462 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.085 (457 hom., cov: 0)
  • Exomes 𝑓: 0.035 (5 hom.)
• Consequence: SEMA3D NM_001384900.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.718
• 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 (AFR) allele frequency at 95% confidence interval = 0.14 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+64_861+71delATATATAT		intron	N/A	NP_001371829.1	O95025
	SEMA3D	NM_001384901.1		c.861+64_861+71delATATATAT		intron	N/A	NP_001371830.1	O95025
	SEMA3D	NM_001384902.1		c.861+64_861+71delATATATAT		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+64_861+71delATATATAT		intron	N/A	ENSP00000284136.6	O95025
	SEMA3D	ENST00000444867.1	TSL:1	c.861+64_861+71delATATATAT		intron	N/A	ENSP00000401366.1	C9JYT6
	SEMA3D	ENST00000916323.1		c.861+64_861+71delATATATAT		intron	N/A	ENSP00000586382.1

Frequencies

GnomAD3 genomes AF: 0.0846 AC: 9432 AN: 111502 Hom.: 457 Cov.: 0

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.0347

Gnomad AMR AF: 0.0648

Gnomad ASJ AF: 0.0523

Gnomad EAS AF: 0.0271

Gnomad SAS AF: 0.0771

Gnomad FIN AF: 0.0793

Gnomad MID AF: 0.0874

Gnomad NFE AF: 0.0633

Gnomad OTH AF: 0.0667

GnomAD4 exome AF: 0.0348 AC: 1669 AN: 47924 Hom.: 5 AF XY: 0.0345 AC XY: 954 AN XY: 27676

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

African (AFR) AF: 0.0838 AC: 57 AN: 680

American (AMR) AF: 0.0417 AC: 32 AN: 768

Ashkenazi Jewish (ASJ) AF: 0.0268 AC: 19 AN: 708

East Asian (EAS) AF: 0.0427 AC: 44 AN: 1030

South Asian (SAS) AF: 0.0295 AC: 30 AN: 1018

European-Finnish (FIN) AF: 0.0421 AC: 53 AN: 1260

Middle Eastern (MID) AF: 0.0169 AC: 2 AN: 118

European-Non Finnish (NFE) AF: 0.0337 AC: 1364 AN: 40490

Other (OTH) AF: 0.0367 AC: 68 AN: 1852

⚠️ 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: 0.0846 AC: 9431 AN: 111504 Hom.: 457 Cov.: 0 AF XY: 0.0846 AC XY: 4375 AN XY: 51738

African (AFR) AF: 0.144 AC: 4357 AN: 30326

American (AMR) AF: 0.0648 AC: 619 AN: 9556

Ashkenazi Jewish (ASJ) AF: 0.0523 AC: 154 AN: 2946

East Asian (EAS) AF: 0.0273 AC: 98 AN: 3594

South Asian (SAS) AF: 0.0767 AC: 229 AN: 2986

European-Finnish (FIN) AF: 0.0793 AC: 288 AN: 3630

Middle Eastern (MID) AF: 0.0859 AC: 17 AN: 198

European-Non Finnish (NFE) AF: 0.0633 AC: 3546 AN: 56024

Other (OTH) AF: 0.0655 AC: 96 AN: 1466

Alfa AF: 0.0854 Hom.: 173

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.72
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;