10-80516226-C-G

Variant names:

• chr10-80516226-C-G
• NM_030927.4:c.644C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030927.4(TSPAN14):​c.644C>G​(p.Ser215Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TSPAN14 NM_030927.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.577
• Publications: 0 publications found

Genes affected

TSPAN14 (HGNC:23303): (tetraspanin 14) Enables enzyme binding activity. Involved in positive regulation of Notch signaling pathway; protein localization to plasma membrane; and protein maturation. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26640618).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030927.4. 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
	TSPAN14	NM_030927.4	MANE Select	c.644C>G	p.Ser215Cys	missense	Exon 8 of 9	NP_112189.2	Q8NG11-1
	TSPAN14	NM_001351266.2		c.644C>G	p.Ser215Cys	missense	Exon 9 of 10	NP_001338195.1	Q8NG11-1
	TSPAN14	NM_001351267.4		c.644C>G	p.Ser215Cys	missense	Exon 10 of 11	NP_001338196.1	Q8NG11-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN14	ENST00000429989.8	TSL:1 MANE Select	c.644C>G	p.Ser215Cys	missense	Exon 8 of 9	ENSP00000396270.2	Q8NG11-1
	TSPAN14	ENST00000372164.7	TSL:1	c.593C>G	p.Ser198Cys	missense	Exon 7 of 8	ENSP00000361237.3	Q8NG11-2
	TSPAN14	ENST00000714439.1		c.686C>G	p.Ser229Cys	missense	Exon 10 of 11	ENSP00000519708.1	A0AAQ5BI32

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	Benign	0.27
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.39	T
Eigen	Benign	-0.0033
Eigen_PC	Benign	-0.067
FATHMM_MKL	Benign	0.41	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.076	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.58
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.44
Sift	Benign	0.18	T
Sift4G	Benign	0.18	T
Polyphen		0.84	P
Vest4		0.27
MutPred		0.53		Loss of disorder (P = 0.0502)
MVP		0.55
MPC		1.5
ClinPred		0.57	D
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.071
gMVP		0.76
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

hg19: chr10-82275982;