NM_198925.4:c.739C>G

Variant names:

• chr15-90221643-C-G
• NM_198925.4:c.739C>G

Variant summary

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

The NM_198925.4(SEMA4B):​c.739C>G​(p.Pro247Ala) 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. 12/19 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: SEMA4B NM_198925.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.30

Genes affected

SEMA4B (HGNC:10730): (semaphorin 4B) Predicted to enable chemorepellent activity and semaphorin receptor binding activity. Predicted to be involved in several processes, including generation of neurons; neural crest cell migration; and semaphorin-plexin signaling pathway. Predicted to be located in plasma membrane. Predicted to be active in extracellular space. Predicted to be 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=0.24645227).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA4B	NM_198925.4	c.739C>G	p.Pro247Ala	missense_variant	Exon 7 of 14	ENST00000411539.7	NP_945119.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA4B	ENST00000411539.7	c.739C>G	p.Pro247Ala	missense_variant	Exon 7 of 14	1	NM_198925.4	ENSP00000394720.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 26, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.739C>G (p.P247A) alteration is located in exon 8 (coding exon 7) of the SEMA4B gene. This alteration results from a C to G substitution at nucleotide position 739, causing the proline (P) at amino acid position 247 to be replaced by an alanine (A). 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	0.086
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.017	T;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Benign	0.40	N
LIST_S2	Uncertain	0.92	.;D
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.12
Sift	Uncertain	0.012	D;D
Sift4G	Benign	0.12	T;T
Vest4		0.38
MVP		0.42
MPC		0.54
ClinPred		0.87	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.44

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: chr15-90764875;