17-30329397-C-T

Variant names:

• chr17-30329397-C-T
• rs1313295169
• NM_206832.3:c.215G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_206832.3(TMIGD1):​c.215G>A​(p.Gly72Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G72A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TMIGD1 NM_206832.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94

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]

ACMG classification

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=0.24148726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMIGD1	NM_206832.3	c.215G>A	p.Gly72Glu	missense_variant	Exon 3 of 7	ENST00000328886.5	NP_996663.1
TMIGD1	NM_001319942.2	c.215G>A	p.Gly72Glu	missense_variant	Exon 3 of 6		NP_001306871.1
TMIGD1	XM_011524787.2	c.215G>A	p.Gly72Glu	missense_variant	Exon 3 of 7		XP_011523089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMIGD1	ENST00000328886.5	c.215G>A	p.Gly72Glu	missense_variant	Exon 3 of 7	1	NM_206832.3	ENSP00000332404.4
TMIGD1	ENST00000538566.6	c.215G>A	p.Gly72Glu	missense_variant	Exon 3 of 6	2		ENSP00000446118.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	.;T
Eigen	Benign	0.045
Eigen_PC	Benign	-0.064
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.8	D;D
REVEL	Benign	0.15
Sift	Benign	0.056	T;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.98	D;D
Vest4		0.34
MutPred		0.43		Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);
MVP		0.23
MPC		0.095
ClinPred		0.97	D
GERP RS		4.5
Varity_R		0.21
gMVP		0.60

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

LitVar

Other links and lift over

dbSNP: rs1313295169; hg19: chr17-28656415;