NM_001370302.1:c.312G>C

Variant names:

• chr12-30978596-G-C
• rs780330970
• NM_001370302.1:c.312G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001370302.1(TSPAN11):​c.312G>C​(p.Glu104Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TSPAN11 NM_001370302.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.40
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.863

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN11	NM_001370302.1	MANE Select	c.312G>C	p.Glu104Asp	missense	Exon 4 of 8	NP_001357231.1	A1L157
	TSPAN11	NM_001080509.3		c.312G>C	p.Glu104Asp	missense	Exon 4 of 8	NP_001073978.1	A1L157
	TSPAN11	NM_001370301.1		c.282G>C	p.Glu94Asp	missense	Exon 3 of 7	NP_001357230.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN11	ENST00000546076.6	TSL:2 MANE Select	c.312G>C	p.Glu104Asp	missense	Exon 4 of 8	ENSP00000437403.1	A1L157
	TSPAN11	ENST00000261177.10	TSL:1	c.312G>C	p.Glu104Asp	missense	Exon 4 of 8	ENSP00000261177.9	A1L157
	TSPAN11	ENST00000851526.1		c.312G>C	p.Glu104Asp	missense	Exon 4 of 8	ENSP00000521585.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251488 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461874 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

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

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60392

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0385499), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	D
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.059	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	0.78	D
MutationAssessor	Pathogenic	3.6	H
PhyloP100		3.4
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.6	D
REVEL	Pathogenic	0.81
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.018	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.63		Gain of catalytic residue at F101 (P = 0.5899)
MVP		0.76
MPC		0.40
ClinPred		0.99	D
GERP RS		3.3
Varity_R		0.87
gMVP		0.92
Mutation Taster		=45/55	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs780330970; hg19: chr12-31131531;