10-80520204-C-T

Variant names:

• chr10-80520204-C-T
• rs873258
• NM_030927.4:c.*2228C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030927.4(TSPAN14):​c.*2228C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 175,682 control chromosomes in the GnomAD database, including 11,606 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (9639 hom., cov: 30)
  • Exomes 𝑓: 0.38 (1967 hom.)
• Consequence: TSPAN14 NM_030927.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.216
• Publications: 14 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN14	NM_030927.4	c.*2228C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000429989.8	NP_112189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPAN14	ENST00000429989.8	c.*2228C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_030927.4	ENSP00000396270.2

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48205 AN: 151560 Hom.: 9641 Cov.: 30

Gnomad AFR AF: 0.0966

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.345

GnomAD4 exome AF: 0.381 AC: 9144 AN: 24004 Hom.: 1967 Cov.: 0 AF XY: 0.378 AC XY: 4768 AN XY: 12614

African (AFR) AF: 0.0870 AC: 43 AN: 494

American (AMR) AF: 0.417 AC: 1158 AN: 2778

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 158 AN: 500

East Asian (EAS) AF: 0.843 AC: 752 AN: 892

South Asian (SAS) AF: 0.313 AC: 993 AN: 3174

European-Finnish (FIN) AF: 0.363 AC: 231 AN: 636

Middle Eastern (MID) AF: 0.435 AC: 40 AN: 92

European-Non Finnish (NFE) AF: 0.373 AC: 5312 AN: 14258

Other (OTH) AF: 0.387 AC: 457 AN: 1180

GnomAD4 genome AF: 0.318 AC: 48186 AN: 151678 Hom.: 9639 Cov.: 30 AF XY: 0.322 AC XY: 23888 AN XY: 74110

African (AFR) AF: 0.0963 AC: 3988 AN: 41408

American (AMR) AF: 0.387 AC: 5894 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1232 AN: 3466

East Asian (EAS) AF: 0.825 AC: 4203 AN: 5092

South Asian (SAS) AF: 0.340 AC: 1629 AN: 4798

European-Finnish (FIN) AF: 0.360 AC: 3783 AN: 10510

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.388 AC: 26296 AN: 67858

Other (OTH) AF: 0.344 AC: 725 AN: 2110

Alfa AF: 0.349 Hom.: 15717

Bravo AF: 0.314

Asia WGS AF: 0.486 AC: 1687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.54
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism (auto)

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: rs873258; hg19: chr10-82279960;