chr1-175079510-A-G

Position:

• chr1-175079510-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022093.2(TNN):​c.587A>G​(p.Asp196Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TNN NM_022093.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.99

Genes affected

TNN (HGNC:22942): (tenascin N) Predicted to enable integrin binding activity. Predicted to be involved in several processes, including generation of neurons; negative regulation of canonical Wnt signaling pathway involved in osteoblast differentiation; and negative regulation of osteoblast differentiation. Predicted to act upstream of or within axonogenesis. Predicted to be located in extracellular matrix and neuron projection. Predicted to be active in collagen-containing extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNN	NM_022093.2	c.587A>G	p.Asp196Gly	missense_variant	3/19	ENST00000239462.9
TNN	XM_017002048.2	c.641A>G	p.Asp214Gly	missense_variant	3/19
TNN	XM_017002049.2	c.641A>G	p.Asp214Gly	missense_variant	3/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNN	ENST00000239462.9	c.587A>G	p.Asp196Gly	missense_variant	3/19	2	NM_022093.2	P1
TNN	ENST00000621086.1	c.587A>G	p.Asp196Gly	missense_variant	2/16	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 31, 2024

The c.587A>G (p.D196G) alteration is located in exon 3 (coding exon 2) of the TNN gene. This alteration results from a A to G substitution at nucleotide position 587, causing the aspartic acid (D) at amino acid position 196 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;.;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.77	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.53	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	M;.;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-6.0	D;.;.
REVEL	Benign	0.17
Sift	Benign	0.047	D;.;.
Sift4G	Uncertain	0.011	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.45
MutPred		0.57		Loss of stability (P = 0.0668);Loss of stability (P = 0.0668);Loss of stability (P = 0.0668);
MVP		0.71
MPC		0.34
ClinPred		0.99	D
GERP RS		3.6
Varity_R		0.57
gMVP		0.80

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: chr1-175048646;