chr1-151142531-G-A

Variant names:

• chr1-151142531-G-A
• rs35817752
• NM_030913.6:c.91C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_030913.6(SEMA6C):​c.91C>T​(p.Leu31Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00825 in 1,613,176 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0085 (61 hom.)
• Consequence: SEMA6C NM_030913.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.468
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00812459).
• BP6: Variant 1-151142531-G-A is Benign according to our data. Variant chr1-151142531-G-A is described in ClinVar as Benign. ClinVar VariationId is 770327.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030913.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6C	NM_030913.6	MANE Select	c.91C>T	p.Leu31Phe	missense	Exon 3 of 19	NP_112175.2
	SEMA6C	NM_001178061.3		c.91C>T	p.Leu31Phe	missense	Exon 3 of 20	NP_001171532.1	Q9H3T2-3
	SEMA6C	NM_001178062.3		c.91C>T	p.Leu31Phe	missense	Exon 3 of 19	NP_001171533.1	Q9H3T2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6C	ENST00000368914.8	TSL:1 MANE Select	c.91C>T	p.Leu31Phe	missense	Exon 3 of 19	ENSP00000357910.3	Q9H3T2-1
	SEMA6C	ENST00000368913.7	TSL:1	c.91C>T	p.Leu31Phe	missense	Exon 3 of 20	ENSP00000357909.3	Q9H3T2-3
	SEMA6C	ENST00000341697.7	TSL:1	c.91C>T	p.Leu31Phe	missense	Exon 3 of 19	ENSP00000344148.3	Q9H3T2-1

Frequencies

GnomAD3 genomes AF: 0.00551 AC: 838 AN: 152174 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00140

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00292

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00967

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00613 AC: 1520 AN: 247824 AF XY: 0.00614

Gnomad AFR exome AF: 0.00144

Gnomad AMR exome AF: 0.00218

Gnomad ASJ exome AF: 0.000614

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00380

Gnomad NFE exome AF: 0.0109

Gnomad OTH exome AF: 0.00555

GnomAD4 exome AF: 0.00853 AC: 12468 AN: 1460884 Hom.: 61 Cov.: 32 AF XY: 0.00838 AC XY: 6092 AN XY: 726680

African (AFR) AF: 0.00120 AC: 40 AN: 33456

American (AMR) AF: 0.00215 AC: 96 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00112 AC: 29 AN: 25918

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00273 AC: 235 AN: 85998

European-Finnish (FIN) AF: 0.00457 AC: 244 AN: 53400

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5764

European-Non Finnish (NFE) AF: 0.0103 AC: 11431 AN: 1111662

Other (OTH) AF: 0.00641 AC: 387 AN: 60346

GnomAD4 genome AF: 0.00550 AC: 838 AN: 152292 Hom.: 3 Cov.: 32 AF XY: 0.00532 AC XY: 396 AN XY: 74464

African (AFR) AF: 0.00140 AC: 58 AN: 41558

American (AMR) AF: 0.00418 AC: 64 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4826

European-Finnish (FIN) AF: 0.00292 AC: 31 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00967 AC: 658 AN: 68020

Other (OTH) AF: 0.00426 AC: 9 AN: 2112

Alfa AF: 0.00850 Hom.: 16

Bravo AF: 0.00530

TwinsUK AF: 0.0102 AC: 38

ALSPAC AF: 0.00882 AC: 34

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.00977 AC: 84

ExAC AF: 0.00693 AC: 841

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00791

EpiControl AF: 0.00896

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.062	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.46	N
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.0081	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.47
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.0090
Sift	Benign	0.036	D
Sift4G	Benign	0.43	T
Polyphen		0.068	B
Vest4		0.34
MVP		0.26
MPC		0.49
ClinPred		0.0074	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.041
gMVP		0.36
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs35817752; hg19: chr1-151115007; COSMIC: COSV99052430; COSMIC: COSV99052430;