Genetic Variant TMIGD1:p.Cys143Phe (chr17-30325028-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_206832.3(TMIGD1):c.428G>T(p.Cys143Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000144 in 1,613,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

TMIGD1
NM_206832.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.10

Publications

4 publications found

Variant links:

Genes affected

TMIGD1 (HGNC:32431): (transmembrane and immunoglobulin domain containing 1) Involved in several processes, including negative regulation of apoptotic process; regulation of cell migration; and regulation of membrane permeability. Located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMIGD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PP3

MetaRNN computational evidence supports a deleterious effect, 0.816

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206832.3. 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
	TMIGD1	NM_206832.3	MANE Select	c.428G>T	p.Cys143Phe	missense	Exon 4 of 7	NP_996663.1	Q6UXZ0-1
	TMIGD1	NM_001319942.2		c.428G>T	p.Cys143Phe	missense	Exon 4 of 6	NP_001306871.1	Q6UXZ0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMIGD1	ENST00000328886.5	TSL:1 MANE Select	c.428G>T	p.Cys143Phe	missense	Exon 4 of 7	ENSP00000332404.4	Q6UXZ0-1
TMIGD1	ENST00000854986.1		c.428G>T	p.Cys143Phe	missense	Exon 4 of 7	ENSP00000525045.1
TMIGD1	ENST00000538566.6	TSL:2	c.428G>T	p.Cys143Phe	missense	Exon 4 of 6	ENSP00000446118.2	Q6UXZ0-2

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000290

AC:

AN:

251294

AF XY:

0.000250

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00427

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000142

AC:

207

AN:

1461816

Hom.:

Cov.:

AF XY:

0.000142

AC XY:

103

AN XY:

727210

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.000358

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00432

AC:

113

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000450

AC:

AN:

1111956

Other (OTH)

AF:

0.000431

AC:

AN:

60390

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

Exome 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

GnomAD4 genome

AF:

0.000164

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41436

American (AMR)

AF:

0.000131

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00461

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5206

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

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:

0.000347

Hom.:

Bravo

AF:

0.000204

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000222

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

Pathogenic

0.91

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Pathogenic

0.35

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.74

M_CAP

Pathogenic

0.48

MetaRNN

Pathogenic

0.82

MetaSVM

Pathogenic

0.96

MutationAssessor

Pathogenic

3.6

PhyloP100

5.1

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-11

REVEL

Pathogenic

0.72

Sift

Uncertain

0.0030

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.95

MVP

0.93

MPC

0.25

ClinPred

0.88

GERP RS

5.8

Varity_R

0.91

gMVP

0.94

Mutation Taster

=11/89

disease causing

(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

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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