chr7-85055645-C-CATATATATATATATAT

Variant names:

• chr7-85055645-C-CATATATATATATATAT
• rs56131427
• NM_001384900.1:c.861+56_861+71dupATATATATATATATAT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001384900.1(SEMA3D):​c.861+56_861+71dupATATATATATATATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000063 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SEMA3D NM_001384900.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• 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: Uncertain_significance. The variant received 0 ACMG points.

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+56_861+71dupATATATATATATATAT		intron	N/A	NP_001371829.1	O95025
	SEMA3D	NM_001384901.1		c.861+56_861+71dupATATATATATATATAT		intron	N/A	NP_001371830.1	O95025
	SEMA3D	NM_001384902.1		c.861+56_861+71dupATATATATATATATAT		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+71_861+72insATATATATATATATAT		intron	N/A	ENSP00000284136.6	O95025
	SEMA3D	ENST00000444867.1	TSL:1	c.861+71_861+72insATATATATATATATAT		intron	N/A	ENSP00000401366.1	C9JYT6
	SEMA3D	ENST00000916323.1		c.861+71_861+72insATATATATATATATAT		intron	N/A	ENSP00000586382.1

Frequencies

GnomAD3 genomes AF: 0.0000627 AC: 7 AN: 111634 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000276

Gnomad SAS AF: 0.000333

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000892

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 48172 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 27812

African (AFR) AF: 0.00 AC: 0 AN: 690

American (AMR) AF: 0.00 AC: 0 AN: 774

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 712

East Asian (EAS) AF: 0.00 AC: 0 AN: 1038

South Asian (SAS) AF: 0.00 AC: 0 AN: 1024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1262

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 118

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 40694

Other (OTH) AF: 0.00 AC: 0 AN: 1860

GnomAD4 genome AF: 0.0000627 AC: 7 AN: 111636 Hom.: 0 Cov.: 0 AF XY: 0.0000579 AC XY: 3 AN XY: 51818

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

African (AFR) AF: 0.00 AC: 0 AN: 30380

American (AMR) AF: 0.00 AC: 0 AN: 9568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2948

East Asian (EAS) AF: 0.000278 AC: 1 AN: 3598

South Asian (SAS) AF: 0.000334 AC: 1 AN: 2992

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3644

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 200

European-Non Finnish (NFE) AF: 0.0000892 AC: 5 AN: 56060

Other (OTH) AF: 0.00 AC: 0 AN: 1468

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0

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;