chr7-84999604-T-C

Position:

• chr7-84999604-T-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.2170A>G​(p.Asn724Asp) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEMA3D NM_001384900.1 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 1.75

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=0.13502946).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3D	NM_001384900.1	c.2170A>G	p.Asn724Asp	missense_variant	19/19	ENST00000284136.11	NP_001371829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3D	ENST00000284136.11	c.2170A>G	p.Asn724Asp	missense_variant	19/19	5	NM_001384900.1	ENSP00000284136	P1
SEMA3D	ENST00000484038.1	n.1296A>G		non_coding_transcript_exon_variant	10/10	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

SEMA3D-related disorder Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 03, 2024

The SEMA3D c.2170A>G variant is predicted to result in the amino acid substitution p.Asn724Asp. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.16
Eigen_PC	Benign	0.059
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
MutationTaster	Benign	0.90	N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.030
Sift	Benign	0.19	T
Sift4G	Benign	0.35	T
Polyphen		0.057	B
Vest4		0.090
MutPred		0.38		Gain of sheet (P = 0.0125);
MVP		0.59
MPC		0.18
ClinPred		0.30	T
GERP RS		5.7
Varity_R		0.21
gMVP		0.20

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

LitVar

Other links and lift over

dbSNP: rs1789598126; hg19: chr7-84628920;