rs145311586

Variant names:

• chr1-31577285-G-A
• rs145311586
• NM_022164.3:c.137G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_022164.3(TINAGL1):​c.137G>A​(p.Arg46Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000527 in 1,612,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R46W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000042 (0 hom.)
• Consequence: TINAGL1 NM_022164.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.26
• Publications: 0 publications found

Genes affected

TINAGL1 (HGNC:19168): (tubulointerstitial nephritis antigen like 1) The protein encoded by this gene is similar in sequence to tubulointerstitial nephritis antigen, a secreted glycoprotein that is recognized by antibodies in some types of immune-related tubulointerstitial nephritis. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]

LINC01226 (HGNC:49678): (long intergenic non-protein coding RNA 1226)

ENSG00000229167 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.034586817).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022164.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TINAGL1	NM_022164.3	MANE Select	c.137G>A	p.Arg46Gln	missense	Exon 2 of 12	NP_071447.1	Q9GZM7-1
	TINAGL1	NM_001204414.2		c.137G>A	p.Arg46Gln	missense	Exon 2 of 11	NP_001191343.1	Q9GZM7-3
	LOC105378626	NR_188670.1		n.54+559C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TINAGL1	ENST00000271064.12	TSL:1 MANE Select	c.137G>A	p.Arg46Gln	missense	Exon 2 of 12	ENSP00000271064.7	Q9GZM7-1
	TINAGL1	ENST00000861777.1		c.137G>A	p.Arg46Gln	missense	Exon 2 of 13	ENSP00000531836.1
	TINAGL1	ENST00000861779.1		c.137G>A	p.Arg46Gln	missense	Exon 2 of 13	ENSP00000531838.1

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152232 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000689 AC: 17 AN: 246764 AF XY: 0.0000522

Gnomad AFR exome AF: 0.000623

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000548

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000273

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000425 AC: 62 AN: 1460416 Hom.: 0 Cov.: 31 AF XY: 0.0000454 AC XY: 33 AN XY: 726556

African (AFR) AF: 0.000657 AC: 22 AN: 33472

American (AMR) AF: 0.0000672 AC: 3 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39686

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1111682

Other (OTH) AF: 0.000315 AC: 19 AN: 60354

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152350 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74510

African (AFR) AF: 0.000529 AC: 22 AN: 41578

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000108 Hom.: 0

Bravo AF: 0.000181

ESP6500AA AF: 0.000909 AC: 4

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000660 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.11	N
PhyloP100		2.3
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.97	N
REVEL	Benign	0.061
Sift	Benign	1.0	T
Sift4G	Benign	0.68	T
Polyphen		0.0080	B
Vest4		0.12
MVP		0.37
MPC		0.54
ClinPred		0.028	T
GERP RS		0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.028
gMVP		0.66
Mutation Taster		=93/7	polymorphism

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: rs145311586; hg19: chr1-32042886; COSMIC: COSV54699252; COSMIC: COSV54699252;