7-16779015-A-G

Position:

• chr7-16779015-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014399.4(TSPAN13):​c.439A>G​(p.Ser147Gly) 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. 16/21 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: TSPAN13 NM_014399.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.68

Genes affected

TSPAN13 (HGNC:21643): (tetraspanin 13) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08539447).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPAN13	NM_014399.4	c.439A>G	p.Ser147Gly	missense_variant	5/6	ENST00000262067.5	NP_055214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPAN13	ENST00000262067.5	c.439A>G	p.Ser147Gly	missense_variant	5/6	1	NM_014399.4	ENSP00000262067	P1
TSPAN13	ENST00000466195.1	n.507A>G		non_coding_transcript_exon_variant	5/5	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 20, 2021

The c.439A>G (p.S147G) alteration is located in exon 5 (coding exon 5) of the TSPAN13 gene. This alteration results from a A to G substitution at nucleotide position 439, causing the serine (S) at amino acid position 147 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	16
DANN	Benign	0.72
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.12
Sift	Benign	0.32	T
Sift4G	Benign	0.34	T
Polyphen		0.017	B
Vest4		0.16
MutPred		0.28		Loss of stability (P = 0.0635);
MVP		0.39
MPC		0.48
ClinPred		0.25	T
GERP RS		4.6
Varity_R		0.081
gMVP		0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-16818640;