Genetic Variant TCAIM:p.Arg217His (chr3-44392932-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_173826.4(TCAIM):c.650G>A(p.Arg217His) variant causes a missense change. The variant allele was found at a frequency of 0.000356 in 1,612,990 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R217G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00037 ( 0 hom. )

Consequence

TCAIM
NM_173826.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.31

Publications

2 publications found

Variant links:

Genes affected

TCAIM (HGNC:25241): (T cell activation inhibitor, mitochondrial) Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

TCAIM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.16858357).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173826.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCAIM	NM_173826.4	MANE Select	c.650G>A	p.Arg217His	missense	Exon 6 of 11	NP_776187.2	Q8N3R3-1
TCAIM	NM_001282913.2		c.650G>A	p.Arg217His	missense	Exon 6 of 11	NP_001269842.1	Q8N3R3-1
TCAIM	NM_001282914.2		c.218G>A	p.Arg73His	missense	Exon 6 of 11	NP_001269843.1	Q8N3R3-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCAIM	ENST00000342649.9	TSL:1 MANE Select	c.650G>A	p.Arg217His	missense	Exon 6 of 11	ENSP00000341539.4	Q8N3R3-1
TCAIM	ENST00000412611.6	TSL:1	n.*226G>A		non_coding_transcript_exon	Exon 6 of 11	ENSP00000392032.2	Q8N3R3-2
TCAIM	ENST00000412611.6	TSL:1	n.*226G>A		3_prime_UTR	Exon 6 of 11	ENSP00000392032.2	Q8N3R3-2

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000235

AC:

AN:

251056

AF XY:

0.000258

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000490

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000343

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000371

AC:

542

AN:

1460784

Hom.:

Cov.:

AF XY:

0.000369

AC XY:

268

AN XY:

726720

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33452

American (AMR)

AF:

0.000112

AC:

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.000253

AC:

AN:

39564

South Asian (SAS)

AF:

0.000151

AC:

AN:

86190

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53360

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.000451

AC:

501

AN:

1111348

Other (OTH)

AF:

0.000215

AC:

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000217

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41532

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000426

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000328

Hom.:

Bravo

AF:

0.000230

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000466

AC:

ExAC

AF:

0.000206

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.15

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.035

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.4

PhyloP100

6.3

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.19

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.015

Polyphen

1.0

Vest4

0.43

MVP

0.67

MPC

0.90

ClinPred

0.48

GERP RS

4.9

Varity_R

0.28

gMVP

0.62

Mutation Taster

=74/26

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over