1-175324397-T-G

Position:

• chr1-175324397-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_003285.3(TNR):​c.3916A>C​(p.Thr1306Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TNR NM_003285.3 missense
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 5.69

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]

ENSG00000260990 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-175324397-T-G is Pathogenic according to our data. Variant chr1-175324397-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 1686264.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNR	NM_003285.3	c.3916A>C	p.Thr1306Pro	missense_variant	22/23	ENST00000367674.7	NP_003276.3
TNR	NM_001328635.2	c.2917A>C	p.Thr973Pro	missense_variant	22/23		NP_001315564.1
LOC105371623	XR_001738299.2	n.231+3276T>G		intron_variant
LOC105371623	XR_001738302.2	n.231+3276T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNR	ENST00000367674.7	c.3916A>C	p.Thr1306Pro	missense_variant	22/23	5	NM_003285.3	ENSP00000356646.1
ENSG00000260990	ENST00000569593.1	n.335+3276T>G		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neurodevelopmental disorder, nonprogressive, with spasticity and transient opisthotonus Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;T
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	.;D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Uncertain	0.12	D
MutationAssessor	Benign	1.4	L;L
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-2.1	N;N
REVEL	Uncertain	0.64
Sift	Uncertain	0.023	D;D
Sift4G	Uncertain	0.024	D;D
Polyphen		1.0	D;D
Vest4		0.59
MutPred		0.83		Loss of MoRF binding (P = 0.0608);Loss of MoRF binding (P = 0.0608);
MVP		0.70
MPC		2.0
ClinPred		0.96	D
GERP RS		5.7
Varity_R		0.75
gMVP		0.95

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-175293533;