Genetic Variant NM_001370302.1:c.518G>C (chr12-30982593-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001370302.1(TSPAN11):c.518G>C(p.Arg173Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 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. R173Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TSPAN11
NM_001370302.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.89

Publications

0 publications found

Variant links:

Genes affected

TSPAN11 (HGNC:30795): (tetraspanin 11) Predicted to be involved in cell migration. Predicted to be integral component of membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TSPAN11 links:

TSPAN11-AS1 (HGNC:56687): (TSPAN11 antisense RNA 1)

TSPAN11-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04482186).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370302.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TSPAN11	NM_001370302.1	MANE Select	c.518G>C	p.Arg173Pro	missense	Exon 6 of 8	NP_001357231.1	A1L157
TSPAN11	NM_001080509.3		c.518G>C	p.Arg173Pro	missense	Exon 6 of 8	NP_001073978.1	A1L157
TSPAN11	NM_001370301.1		c.488G>C	p.Arg163Pro	missense	Exon 5 of 7	NP_001357230.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TSPAN11	ENST00000546076.6	TSL:2 MANE Select	c.518G>C	p.Arg173Pro	missense	Exon 6 of 8	ENSP00000437403.1	A1L157
TSPAN11	ENST00000261177.10	TSL:1	c.518G>C	p.Arg173Pro	missense	Exon 6 of 8	ENSP00000261177.9	A1L157
TSPAN11	ENST00000851526.1		c.518G>C	p.Arg173Pro	missense	Exon 6 of 8	ENSP00000521585.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460656

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726612

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52532

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111804

Other (OTH)

AF:

0.00

AC:

AN:

60366

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

0.0030

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.079

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0087

LIST_S2

Benign

0.18

M_CAP

Benign

0.015

MetaRNN

Benign

0.045

MetaSVM

Benign

-0.89

MutationAssessor

Benign

-0.56

PhyloP100

-1.9

PrimateAI

Benign

0.33

PROVEAN

Benign

0.14

REVEL

Benign

0.25

Sift

Benign

0.32

Sift4G

Benign

0.31

Polyphen

0.0

Vest4

0.094

MutPred

0.61

Gain of catalytic residue at R173 (P = 0.0784)

MVP

0.12

MPC

0.11

ClinPred

0.084

GERP RS

-8.0

Varity_R

0.11

gMVP

0.78

Mutation Taster

=89/11

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over