chr10-80516235-C-T

Variant names:

• chr10-80516235-C-T
• rs201180720
• NM_030927.4:c.653C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_030927.4(TSPAN14):​c.653C>T​(p.Thr218Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,614,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: TSPAN14 NM_030927.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.76
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.26252168).

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.653C>T	p.Thr218Met	missense	Exon 8 of 9	NP_112189.2	Q8NG11-1
	TSPAN14	NM_001351266.2		c.653C>T	p.Thr218Met	missense	Exon 9 of 10	NP_001338195.1	Q8NG11-1
	TSPAN14	NM_001351267.4		c.653C>T	p.Thr218Met	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.653C>T	p.Thr218Met	missense	Exon 8 of 9	ENSP00000396270.2	Q8NG11-1
	TSPAN14	ENST00000372164.7	TSL:1	c.602C>T	p.Thr201Met	missense	Exon 7 of 8	ENSP00000361237.3	Q8NG11-2
	TSPAN14	ENST00000714439.1		c.695C>T	p.Thr232Met	missense	Exon 10 of 11	ENSP00000519708.1	A0AAQ5BI32

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000119 AC: 30 AN: 251490 AF XY: 0.000155

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000117 AC: 171 AN: 1461886 Hom.: 0 Cov.: 31 AF XY: 0.000128 AC XY: 93 AN XY: 727246

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

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

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

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

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5766

European-Non Finnish (NFE) AF: 0.000129 AC: 144 AN: 1112010

Other (OTH) AF: 0.0000993 AC: 6 AN: 60396

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152344 Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12 AN XY: 74502

African (AFR) AF: 0.0000481 AC: 2 AN: 41586

American (AMR) AF: 0.000392 AC: 6 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000981 Hom.: 0

Bravo AF: 0.000121

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000132 AC: 16

EpiCase AF: 0.000273

EpiControl AF: 0.000237

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	0.15
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T
Eigen	Benign	0.19
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.077	D
MetaRNN	Benign	0.26	T
MetaSVM	Uncertain	0.23	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.8
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.030	D
Polyphen		0.10	B
Vest4		0.24
MVP		0.83
MPC		0.87
ClinPred		0.12	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.83
Mutation Taster		=77/23	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

dbSNP: rs201180720; hg19: chr10-82275991;