9-89379092-C-G

Variant names:

• chr9-89379092-C-G
• rs374118848
• NM_001371194.2:c.2201G>C

Variant summary

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

The NM_001371194.2(SEMA4D):​c.2201G>C​(p.Arg734Pro) 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. 12/21 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: 33)
• Consequence: SEMA4D NM_001371194.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.217

Genes affected

SEMA4D (HGNC:10732): (semaphorin 4D) Enables identical protein binding activity; semaphorin receptor binding activity; and transmembrane signaling receptor activity. Involved in several processes, including positive regulation of phosphatidylinositol 3-kinase signaling; regulation of neuron projection development; and regulation of phosphate metabolic process. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.15647566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA4D	NM_001371194.2	c.2201G>C	p.Arg734Pro	missense_variant	Exon 16 of 16	ENST00000422704.7	NP_001358123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA4D	ENST00000422704.7	c.2201G>C	p.Arg734Pro	missense_variant	Exon 16 of 16	1	NM_001371194.2	ENSP00000388768.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.16	T;T;T;T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.82	.;.;T;.
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.2	M;M;M;M
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.93	N;N;N;N
REVEL	Uncertain	0.44
Sift	Benign	0.079	T;T;T;T
Sift4G	Benign	0.23	T;T;T;T
Polyphen		0.34	B;B;B;B
Vest4		0.32
MutPred		0.35		Gain of ubiquitination at K729 (P = 0.038);Gain of ubiquitination at K729 (P = 0.038);Gain of ubiquitination at K729 (P = 0.038);Gain of ubiquitination at K729 (P = 0.038);
MVP		0.65
MPC		0.57
ClinPred		0.18	T
GERP RS		3.6
Varity_R		0.23
gMVP		0.58

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: rs374118848; hg19: chr9-91994007;