rs199840599

Variant names:

• chr1-31577270-G-A
• rs199840599
• NM_022164.3:c.122G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-31577270-G-A
• chr1-31577270-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_022164.3(TINAGL1):​c.122G>A​(p.Arg41Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000138 in 1,611,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: TINAGL1 NM_022164.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.01
• Publications: 2 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]

ENSG00000229167 (HGNC:):

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16503274).

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.122G>A	p.Arg41Gln	missense	Exon 2 of 12	NP_071447.1	Q9GZM7-1
	TINAGL1	NM_001204414.2		c.122G>A	p.Arg41Gln	missense	Exon 2 of 11	NP_001191343.1	Q9GZM7-3
	LOC105378626	NR_188670.1		n.54+574C>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.122G>A	p.Arg41Gln	missense	Exon 2 of 12	ENSP00000271064.7	Q9GZM7-1
	TINAGL1	ENST00000861777.1		c.122G>A	p.Arg41Gln	missense	Exon 2 of 13	ENSP00000531836.1
	TINAGL1	ENST00000861779.1		c.122G>A	p.Arg41Gln	missense	Exon 2 of 13	ENSP00000531838.1

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 35 AN: 152230 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000196 AC: 48 AN: 244744 AF XY: 0.000173

Gnomad AFR exome AF: 0.0000634

Gnomad AMR exome AF: 0.000407

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000496

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000184

Gnomad OTH exome AF: 0.000664

GnomAD4 exome AF: 0.000128 AC: 187 AN: 1459544 Hom.: 0 Cov.: 31 AF XY: 0.000149 AC XY: 108 AN XY: 726122

African (AFR) AF: 0.000568 AC: 19 AN: 33468

American (AMR) AF: 0.000358 AC: 16 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39674

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52002

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5762

European-Non Finnish (NFE) AF: 0.0000909 AC: 101 AN: 1111412

Other (OTH) AF: 0.000448 AC: 27 AN: 60328

GnomAD4 genome AF: 0.000230 AC: 35 AN: 152348 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74500

African (AFR) AF: 0.0000722 AC: 3 AN: 41580

American (AMR) AF: 0.00111 AC: 17 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68028

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000293 Hom.: 0

Bravo AF: 0.000249

ExAC AF: 0.000140 AC: 17

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000237

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	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.024	T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	2.0	M
PhyloP100		5.0
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.23
Sift	Benign	0.34	T
Sift4G	Benign	0.60	T
Polyphen		1.0	D
Vest4		0.46
MVP		0.65
MPC		1.4
ClinPred		0.12	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.12
gMVP		0.75
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs199840599; hg19: chr1-32042871; COSMIC: COSV54699496; COSMIC: COSV54699496;