10-80489284-C-T

Variant names:

• chr10-80489284-C-T
• rs79788502
• NM_030927.4:c.51C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_030927.4(TSPAN14):​c.51C>T​(p.Tyr17Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000765 in 1,582,462 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0041 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (4 hom.)
• Consequence: TSPAN14 NM_030927.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.620
• 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: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 10-80489284-C-T is Benign according to our data. Variant chr10-80489284-C-T is described in ClinVar as Benign. ClinVar VariationId is 714487.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.62 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.51C>T	p.Tyr17Tyr	synonymous	Exon 2 of 9	NP_112189.2	Q8NG11-1
	TSPAN14	NM_001351266.2		c.51C>T	p.Tyr17Tyr	synonymous	Exon 3 of 10	NP_001338195.1	Q8NG11-1
	TSPAN14	NM_001351267.4		c.51C>T	p.Tyr17Tyr	synonymous	Exon 4 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.51C>T	p.Tyr17Tyr	synonymous	Exon 2 of 9	ENSP00000396270.2	Q8NG11-1
	TSPAN14	ENST00000372164.7	TSL:1	c.51C>T	p.Tyr17Tyr	synonymous	Exon 2 of 8	ENSP00000361237.3	Q8NG11-2
	TSPAN14	ENST00000714439.1		c.51C>T	p.Tyr17Tyr	synonymous	Exon 3 of 11	ENSP00000519708.1	A0AAQ5BI32

Frequencies

GnomAD3 genomes AF: 0.00406 AC: 618 AN: 152238 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0144

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00109 AC: 220 AN: 201906 AF XY: 0.000725

Gnomad AFR exome AF: 0.0153

Gnomad AMR exome AF: 0.000480

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000231

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000415 AC: 593 AN: 1430106 Hom.: 4 Cov.: 29 AF XY: 0.000352 AC XY: 249 AN XY: 708216

African (AFR) AF: 0.0144 AC: 479 AN: 33172

American (AMR) AF: 0.000523 AC: 21 AN: 40122

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25546

East Asian (EAS) AF: 0.00 AC: 0 AN: 38926

South Asian (SAS) AF: 0.0000733 AC: 6 AN: 81846

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.0000210 AC: 23 AN: 1094330

Other (OTH) AF: 0.00108 AC: 64 AN: 59282

GnomAD4 genome AF: 0.00406 AC: 618 AN: 152356 Hom.: 2 Cov.: 32 AF XY: 0.00391 AC XY: 291 AN XY: 74498

African (AFR) AF: 0.0144 AC: 600 AN: 41592

American (AMR) AF: 0.000784 AC: 12 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68040

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00166 Hom.: 0

Bravo AF: 0.00456

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.1
DANN	Benign	0.45
PhyloP100		0.62
PromoterAI		-0.048	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs79788502; hg19: chr10-82249040;