10-80512244-T-A

Variant names:

• chr10-80512244-T-A
• rs752141874
• NM_030927.4:c.551T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_030927.4(TSPAN14):​c.551T>A​(p.Phe184Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,613,952 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: TSPAN14 NM_030927.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.92
• Publications: 1 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.551T>A	p.Phe184Tyr	missense	Exon 6 of 9	NP_112189.2	Q8NG11-1
	TSPAN14	NM_001351266.2		c.551T>A	p.Phe184Tyr	missense	Exon 7 of 10	NP_001338195.1	Q8NG11-1
	TSPAN14	NM_001351267.4		c.551T>A	p.Phe184Tyr	missense	Exon 8 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.551T>A	p.Phe184Tyr	missense	Exon 6 of 9	ENSP00000396270.2	Q8NG11-1
	TSPAN14	ENST00000372164.7	TSL:1	c.500T>A	p.Phe167Tyr	missense	Exon 5 of 8	ENSP00000361237.3	Q8NG11-2
	TSPAN14	ENST00000714439.1		c.593T>A	p.Phe198Tyr	missense	Exon 8 of 11	ENSP00000519708.1	A0AAQ5BI32

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152206 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251366 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1461746 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727168

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5662

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152206 Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2 AN XY: 74366

African (AFR) AF: 0.0000241 AC: 1 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000416

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	Benign	0.30
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.077	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Uncertain	0.068	D
MutationAssessor	Benign	1.1	L
PhyloP100		7.9
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.63
Sift	Benign	0.14	T
Sift4G	Benign	0.16	T
Polyphen		0.41	B
Vest4		0.73
MutPred		0.54		Gain of ubiquitination at K179 (P = 0.1108)
MVP		0.64
MPC		1.8
ClinPred		0.48	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.47
gMVP		0.81
Mutation Taster		=27/73	disease causing

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

dbSNP: rs752141874; hg19: chr10-82272000;