rs372580265

Variant names:

• chr1-46184396-C-A
• NM_005727.4:c.263C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-46184396-C-A
• chr1-46184396-C-G
• chr1-46184396-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_005727.4(TSPAN1):​c.263C>A​(p.Thr88Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. T88M) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TSPAN1 NM_005727.4 missense, splice_region
• Scores: Splicing: ADA: 0.0001121
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.611

Genes affected

TSPAN1 (HGNC:20657): (tetraspanin 1) 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.897

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN1	NM_005727.4	c.263C>A	p.Thr88Lys	missense_variant, splice_region_variant	Exon 4 of 9	ENST00000372003.6	NP_005718.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPAN1	ENST00000372003.6	c.263C>A	p.Thr88Lys	missense_variant, splice_region_variant	Exon 4 of 9	1	NM_005727.4	ENSP00000361072.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461774 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727168

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.57	D
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	-0.037	T
MutationAssessor	Pathogenic	3.1	M
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.52
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.038	D
Polyphen		0.97	D
Vest4		0.55
MutPred		0.89		Gain of ubiquitination at T88 (P = 0.0203);
MVP		0.62
MPC		0.70
ClinPred		0.90	D
GERP RS		-5.7
Varity_R		0.78
gMVP		0.87

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
dbscSNV1_RF	Benign	0.22
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: chr1-46650068;