7-84999660-A-G

Variant names:

• chr7-84999660-A-G
• NM_001384900.1:c.2114T>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.2114T>C​(p.Leu705Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SEMA3D NM_001384900.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.58

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=0.10384771).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3D	NM_001384900.1	c.2114T>C	p.Leu705Pro	missense_variant	Exon 19 of 19	ENST00000284136.11	NP_001371829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3D	ENST00000284136.11	c.2114T>C	p.Leu705Pro	missense_variant	Exon 19 of 19	5	NM_001384900.1	ENSP00000284136.6
SEMA3D	ENST00000484038.1	n.1240T>C		non_coding_transcript_exon_variant	Exon 10 of 10	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461808 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727212

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.0029	T
Eigen	Benign	-0.22
Eigen_PC	Benign	0.0016
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.58	N
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.36	N
REVEL	Benign	0.067
Sift	Benign	0.31	T
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.23
MutPred		0.47		Gain of sheet (P = 0.0028);
MVP		0.42
MPC		0.25
ClinPred		0.33	T
GERP RS		4.6
Varity_R		0.21
gMVP		0.63

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: chr7-84628976;