9-137192249-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001128228.3(TPRN):c.2073+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000233 in 1,460,828 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: TPRN NM_001128228.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.47

Genes affected

TPRN (HGNC:26894): (taperin) This locus encodes a sensory epithelial protein. It was defined by linkage analysis in three Pakistani families to lie between D9S1818 (centromeric) and D9SH6 (telomeric). Mutations at this locus have been associated with autosomal recessive deafness. [provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054820716).
• BP6: Variant 9-137192249-C-T is Benign according to our data. Variant chr9-137192249-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 505247.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPRN	NM_001128228.3	c.2073+10G>A		intron_variant		ENST00000409012.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPRN	ENST00000409012.6	c.2073+10G>A		intron_variant		1	NM_001128228.3	P1
TPRN	ENST00000477345.1	n.2794+10G>A		intron_variant, non_coding_transcript_variant		1
TPRN	ENST00000333046.8	c.1477G>A	p.Gly493Arg	missense_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000479 AC: 12 AN: 250276 Hom.: 0 AF XY: 0.0000442 AC XY: 6 AN XY: 135690

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000355

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000233 AC: 34 AN: 1460828 Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21 AN XY: 726740

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000894

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000144

Gnomad4 OTH exome AF: 0.0000497

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000223 Hom.: 0

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000412 AC: 5

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 04, 2016

c.2073+10G>A in intron 3 of TPRN: This variant is not expected to have clinical significance because it is not located within the splice consensus sequence. It has been identified in 5/119713 total chromosomes by the Exome Aggregation Cons ortium (ExAC, http://exac.broadinstitute.org; dbSNP rs368771637). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	0.38
Dann	Benign	0.96
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N
PROVEAN	Benign	0.30	N
REVEL	Benign	0.023
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.031	D
MutPred		0.40		Gain of MoRF binding (P = 0.014);
MVP		0.030
ClinPred		0.048	T
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs368771637; hg19: chr9-140086701;