Variant 17-30329376-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_206832.3(TMIGD1):c.236G>C(p.Gly79Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TMIGD1
NM_206832.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.457

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15199715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TMIGD1	NM_206832.3 linkuse as main transcript	c.236G>C	p.Gly79Ala	missense_variant	3/7	ENST00000328886.5	NP_996663.1
TMIGD1	NM_001319942.2 linkuse as main transcript	c.236G>C	p.Gly79Ala	missense_variant	3/6		NP_001306871.1
TMIGD1	XM_011524787.2 linkuse as main transcript	c.236G>C	p.Gly79Ala	missense_variant	3/7		XP_011523089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMIGD1	ENST00000328886.5 linkuse as main transcript	c.236G>C	p.Gly79Ala	missense_variant	3/7	1	NM_206832.3	ENSP00000332404	P1	Q6UXZ0-1
TMIGD1	ENST00000538566.6 linkuse as main transcript	c.236G>C	p.Gly79Ala	missense_variant	3/6	2		ENSP00000446118		Q6UXZ0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2022

The c.236G>C (p.G79A) alteration is located in exon 3 (coding exon 2) of the TMIGD1 gene. This alteration results from a G to C substitution at nucleotide position 236, causing the glycine (G) at amino acid position 79 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.17

.;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.098

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.8

D;D

REVEL

Benign

0.095

Sift

Benign

0.074

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.97

D;D

Vest4

0.18

MutPred

0.23

Loss of ubiquitination at K77 (P = 0.0738);Loss of ubiquitination at K77 (P = 0.0738);

MVP

0.10

MPC

0.035

ClinPred

0.74

GERP RS

-3.9

Varity_R

0.19

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over