1-175330098-T-G

Position:

chr1-175330098-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_003285.3(TNR):c.3769A>C(p.Ile1257Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 1,602,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

TNR
NM_003285.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0880

Variant links:

Genes affected

TNR (HGNC:11953): (tenascin R) This gene encodes a member of the tenascin family of extracellular matrix glycoproteins. The encoded protein is restricted to the central nervous system. The protein may play a role in neurite outgrowth, neural cell adhesion and modulation of sodium channel function. It is a constituent of perineuronal nets. [provided by RefSeq, Aug 2013]

TNR links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09271756).

BP6

Variant 1-175330098-T-G is Benign according to our data. Variant chr1-175330098-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2526264.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0000166 (24/1450088) while in subpopulation EAS AF= 0.00061 (24/39332). AF 95% confidence interval is 0.00042. There are 0 homozygotes in gnomad4_exome. There are 12 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High AC in GnomAdExome4 at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TNR	NM_003285.3 linkuse as main transcript	c.3769A>C	p.Ile1257Leu	missense_variant	21/23	ENST00000367674.7
LOC105371623	XR_001738299.2 linkuse as main transcript	n.318+588T>G		intron_variant, non_coding_transcript_variant
TNR	NM_001328635.2 linkuse as main transcript	c.2770A>C	p.Ile924Leu	missense_variant	21/23
LOC105371623	XR_001738302.2 linkuse as main transcript	n.232-3224T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNR	ENST00000367674.7 linkuse as main transcript	c.3769A>C	p.Ile1257Leu	missense_variant	21/23	5	NM_003285.3	P1	Q92752-1
	ENST00000569593.1 linkuse as main transcript	n.336-279T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000321

AC:

AN:

249322

Hom.:

AF XY:

0.0000297

AC XY:

AN XY:

134726

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000437

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000166

AC:

AN:

1450088

Hom.:

Cov.:

AF XY:

0.0000167

AC XY:

AN XY:

719014

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000610

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000494

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 17, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.46

CADD

Benign

0.48

DANN

Benign

0.85

DEOGEN2

Benign

0.18

T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.64

.;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.093

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.16

N;N

MutationTaster

Benign

0.98

D;D

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.9

N;N

REVEL

Uncertain

0.34

Sift

Benign

0.094

T;T

Sift4G

Benign

0.068

T;T

Polyphen

0.0

B;B

Vest4

0.16

MutPred

0.77

Gain of methylation at R1256 (P = 0.0629);Gain of methylation at R1256 (P = 0.0629);

MVP

0.63

MPC

0.76

ClinPred

0.043

GERP RS

-11

Varity_R

0.14

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over