Genetic Variant NM_206832.3:c.385G>A (chr17-30325071-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_206832.3(TMIGD1):c.385G>A(p.Asp129Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00008 in 1,613,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000083 ( 0 hom. )

Consequence

TMIGD1
NM_206832.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.383

Publications

1 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: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040591).

BP6

Variant 17-30325071-C-T is Benign according to our data. Variant chr17-30325071-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3179790.Status of the report is criteria_provided_single_submitter, 1 stars.

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.385G>A	p.Asp129Asn	missense	Exon 4 of 7	NP_996663.1	Q6UXZ0-1
	TMIGD1	NM_001319942.2		c.385G>A	p.Asp129Asn	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.385G>A	p.Asp129Asn	missense	Exon 4 of 7	ENSP00000332404.4	Q6UXZ0-1
TMIGD1	ENST00000854986.1		c.385G>A	p.Asp129Asn	missense	Exon 4 of 7	ENSP00000525045.1
TMIGD1	ENST00000538566.6	TSL:2	c.385G>A	p.Asp129Asn	missense	Exon 4 of 6	ENSP00000446118.2	Q6UXZ0-2

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000319

AC:

AN:

250930

AF XY:

0.0000442

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000617

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000828

AC:

121

AN:

1461048

Hom.:

Cov.:

AF XY:

0.0000949

AC XY:

AN XY:

726760

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33414

American (AMR)

AF:

0.0000224

AC:

AN:

44652

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86122

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000103

AC:

115

AN:

1111532

Other (OTH)

AF:

0.0000331

AC:

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

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:

0.0000526

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41444

American (AMR)

AF:

0.000131

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

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:

0.0000966

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.11

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.4

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.038

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.63

M_CAP

Benign

0.013

MetaRNN

Benign

0.041

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.2

PhyloP100

0.38

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.1

REVEL

Benign

0.068

Sift

Benign

0.30

Sift4G

Benign

0.071

Polyphen

0.0010

Vest4

0.20

MVP

0.18

MPC

0.027

ClinPred

0.024

GERP RS

-0.98

Varity_R

0.042

gMVP

0.31

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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