7-85055645-CATATATATATATATATATATATATATATAT-CATATATATATATATATATATATATATATATATATATATATAT

Variant names:

• chr7-85055645-C-CATATATATATAT
• rs56131427
• NM_001384900.1:c.861+60_861+71dupATATATATATAT

Variant summary

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

The NM_001384900.1(SEMA3D):​c.861+60_861+71dupATATATATATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000332 in 159,794 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00046 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000042 (0 hom.)
• 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+60_861+71dupATATATATATAT		intron	N/A	NP_001371829.1	O95025
	SEMA3D	NM_001384901.1		c.861+60_861+71dupATATATATATAT		intron	N/A	NP_001371830.1	O95025
	SEMA3D	NM_001384902.1		c.861+60_861+71dupATATATATATAT		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+72insATATATATATAT		intron	N/A	ENSP00000284136.6	O95025
	SEMA3D	ENST00000444867.1	TSL:1	c.861+71_861+72insATATATATATAT		intron	N/A	ENSP00000401366.1	C9JYT6
	SEMA3D	ENST00000916323.1		c.861+71_861+72insATATATATATAT		intron	N/A	ENSP00000586382.1

Frequencies

GnomAD3 genomes AF: 0.000457 AC: 51 AN: 111620 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000165

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000940

Gnomad ASJ AF: 0.000339

Gnomad EAS AF: 0.00138

Gnomad SAS AF: 0.000999

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000482

Gnomad OTH AF: 0.000688

GnomAD4 exome AF: 0.0000415 AC: 2 AN: 48172 Hom.: 0 AF XY: 0.0000360 AC XY: 1 AN XY: 27812

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

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: 0.000792 AC: 1 AN: 1262

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

European-Non Finnish (NFE) AF: 0.0000246 AC: 1 AN: 40694

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

⚠️ 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: 0.000457 AC: 51 AN: 111622 Hom.: 0 Cov.: 0 AF XY: 0.000502 AC XY: 26 AN XY: 51816

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

African (AFR) AF: 0.000165 AC: 5 AN: 30378

American (AMR) AF: 0.000940 AC: 9 AN: 9570

Ashkenazi Jewish (ASJ) AF: 0.000339 AC: 1 AN: 2948

East Asian (EAS) AF: 0.00139 AC: 5 AN: 3598

South Asian (SAS) AF: 0.00100 AC: 3 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: 0.000482 AC: 27 AN: 56048

Other (OTH) AF: 0.000682 AC: 1 AN: 1466

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000513714), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 173

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;