7-84999854-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001384900.1(SEMA3D):c.1920T>G(p.Asp640Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEMA3D NM_001384900.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0270

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13795221).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA3D	NM_001384900.1	c.1920T>G	p.Asp640Glu	missense_variant	19/19	ENST00000284136.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA3D	ENST00000284136.11	c.1920T>G	p.Asp640Glu	missense_variant	19/19	5	NM_001384900.1	P1
SEMA3D	ENST00000484038.1	n.1046T>G		non_coding_transcript_exon_variant	10/10	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 10, 2023

The c.1920T>G (p.D640E) alteration is located in exon 17 (coding exon 17) of the SEMA3D gene. This alteration results from a T to G substitution at nucleotide position 1920, causing the aspartic acid (D) at amino acid position 640 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	18
Dann	Uncertain	0.99
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.059
Eigen_PC	Benign	0.034
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.16
Sift	Benign	0.33	T
Sift4G	Benign	0.29	T
Polyphen		0.40	B
Vest4		0.053
MutPred		0.23		Loss of ubiquitination at K645 (P = 0.0653);
MVP		0.60
MPC		0.36
ClinPred		0.91	D
GERP RS		3.9
Varity_R		0.22
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-84629170;