1-151134828-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030913.6(SEMA6C):c.1628G>C(p.Arg543Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00398 in 1,614,184 control chromosomes in the GnomAD database, including 218 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (102 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (116 hom.)
• Consequence: SEMA6C NM_030913.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0370

Genes affected

SEMA6C (HGNC:10740): (semaphorin 6C) This gene encodes a member of the semaphorin family. Semaphorins represent important molecular signals controlling multiple aspects of the cellular response that follows CNS injury, and thus may play an important role in neural regeneration. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017738342).
• BP6: Variant 1-151134828-C-G is Benign according to our data. Variant chr1-151134828-C-G is described in ClinVar as [Benign]. Clinvar id is 767698.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA6C	NM_030913.6	c.1628G>C	p.Arg543Thr	missense_variant	16/19	ENST00000368914.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA6C	ENST00000368914.8	c.1628G>C	p.Arg543Thr	missense_variant	16/19	1	NM_030913.6	P4

Frequencies

GnomAD3 genomes AF: 0.0210 AC: 3200 AN: 152200 Hom.: 102 Cov.: 32

Gnomad AFR AF: 0.0725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00994

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0143

GnomAD3 exomes AF: 0.00565 AC: 1421 AN: 251472 Hom.: 60 AF XY: 0.00411 AC XY: 559 AN XY: 135908

Gnomad AFR exome AF: 0.0779

Gnomad AMR exome AF: 0.00341

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000193

Gnomad OTH exome AF: 0.00195

GnomAD4 exome AF: 0.00219 AC: 3208 AN: 1461866 Hom.: 116 Cov.: 32 AF XY: 0.00189 AC XY: 1371 AN XY: 727238

Gnomad4 AFR exome AF: 0.0772

Gnomad4 AMR exome AF: 0.00385

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000174

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000129

Gnomad4 OTH exome AF: 0.00449

GnomAD4 genome AF: 0.0211 AC: 3209 AN: 152318 Hom.: 102 Cov.: 32 AF XY: 0.0207 AC XY: 1542 AN XY: 74482

Gnomad4 AFR AF: 0.0725

Gnomad4 AMR AF: 0.00993

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.00160 Hom.: 5

Bravo AF: 0.0242

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.0794 AC: 350

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00703 AC: 854

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 21, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.96
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.82	T;T;.;D
MetaRNN	Benign	0.0018	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;.;M;M
MutationTaster	Benign	0.95	N;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Benign	0.024
Sift	Benign	0.12	T;T;T;T
Sift4G	Uncertain	0.035	D;D;D;D
Polyphen		0.013	B;B;B;B
Vest4		0.50
MVP		0.66
MPC		0.97
ClinPred		0.015	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.087
gMVP		0.47

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs74127528; hg19: chr1-151107304;