chr15-81002651-C-G

Variant names:

• chr15-81002651-C-G
• rs770076998
• NM_022566.3:c.380C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_022566.3(TLNRD1):​c.380C>G​(p.Ala127Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000756 in 1,321,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A127V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: TLNRD1 NM_022566.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.94
• Publications: 0 publications found

Genes affected

TLNRD1 (HGNC:13519): (talin rod domain containing 1) This gene encodes a protein that is regulated by micro RNA MiR-574-3, and is thought to have an oncogenic function in human bladder cancer. A similar gene in mouse is located in a chromosomal region critical for differentiation of mesoderm, which affects embryo patterning and the formation of heart, muscle, blood, skeleton and the urogenital system. The mouse gene is expressed in early development, and in the adult. [provided by RefSeq, Nov 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37397206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLNRD1	NM_022566.3	c.380C>G	p.Ala127Gly	missense_variant	Exon 1 of 1	ENST00000267984.4	NP_072088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLNRD1	ENST00000267984.4	c.380C>G	p.Ala127Gly	missense_variant	Exon 1 of 1	6	NM_022566.3	ENSP00000267984.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.56e-7 AC: 1 AN: 1321994 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 649114

African (AFR) AF: 0.00 AC: 0 AN: 26824

American (AMR) AF: 0.00 AC: 0 AN: 23162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19268

East Asian (EAS) AF: 0.00 AC: 0 AN: 34904

South Asian (SAS) AF: 0.00 AC: 0 AN: 67760

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32798

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5262

European-Non Finnish (NFE) AF: 9.46e-7 AC: 1 AN: 1057150

Other (OTH) AF: 0.00 AC: 0 AN: 54866

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.1	T
PhyloP100		6.9
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.26
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.037	D
Polyphen		0.99	D
Vest4		0.49
MutPred		0.41		Gain of catalytic residue at A127 (P = 0.0357);
MVP		0.14
MPC		1.7
ClinPred		0.97	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.68
gMVP		0.46

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

Other links and lift over

dbSNP: rs770076998; hg19: chr15-81294992;