rs534671276

Variant names:

• chr9-89388673-C-A
• rs534671276
• NM_001371194.2:c.1070G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-89388673-C-A
• chr9-89388673-C-G
• chr9-89388673-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001371194.2(SEMA4D):​c.1070G>T​(p.Arg357Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000207 in 1,451,974 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R357H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SEMA4D NM_001371194.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.65

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA4D	NM_001371194.2	c.1070G>T	p.Arg357Leu	missense_variant	Exon 11 of 16	ENST00000422704.7	NP_001358123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA4D	ENST00000422704.7	c.1070G>T	p.Arg357Leu	missense_variant	Exon 11 of 16	1	NM_001371194.2	ENSP00000388768.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1451974 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 722586

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 33154

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 42820

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 25802

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39650

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 85596

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 48784

Gnomad4 NFE exome AF: 0.00000270 AC: 3 AN: 1110328

Gnomad4 Remaining exome AF: 0.00 AC: 0 AN: 60100

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	.;.;.;T;T;T;T
Eigen	Benign	0.066
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.89	.;D;.;.;.;D;.
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.58	D;D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;M;M;M;M;M;M
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.5	D;D;D;D;D;D;D
REVEL	Benign	0.12
Sift	Uncertain	0.026	D;D;D;D;D;D;D
Sift4G	Benign	0.062	T;T;T;T;T;T;T
Polyphen		0.0080	B;B;B;B;B;B;B
Vest4		0.76
MutPred		0.64		Loss of MoRF binding (P = 0.0034);Loss of MoRF binding (P = 0.0034);Loss of MoRF binding (P = 0.0034);Loss of MoRF binding (P = 0.0034);Loss of MoRF binding (P = 0.0034);Loss of MoRF binding (P = 0.0034);Loss of MoRF binding (P = 0.0034);
MVP		0.40
MPC		0.40
ClinPred		0.98	D
GERP RS		4.7
Varity_R		0.81
gMVP		0.73
Mutation Taster		=17/83	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs534671276; hg19: chr9-92003588;