17-30332087-A-G

Position:

• chr17-30332087-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The ENST00000328886.5(TMIGD1):​c.47T>C​(p.Leu16Pro) 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 pathogenic 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. L16H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMIGD1 ENST00000328886.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.82

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.877

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMIGD1	NM_206832.3	c.47T>C	p.Leu16Pro	missense_variant	2/7	ENST00000328886.5	NP_996663.1
TMIGD1	NM_001319942.2	c.47T>C	p.Leu16Pro	missense_variant	2/6		NP_001306871.1
TMIGD1	XM_011524787.2	c.47T>C	p.Leu16Pro	missense_variant	2/7		XP_011523089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMIGD1	ENST00000328886.5	c.47T>C	p.Leu16Pro	missense_variant	2/7	1	NM_206832.3	ENSP00000332404.4
TMIGD1	ENST00000538566.6	c.47T>C	p.Leu16Pro	missense_variant	2/6	2		ENSP00000446118.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2023

The c.47T>C (p.L16P) alteration is located in exon 2 (coding exon 1) of the TMIGD1 gene. This alteration results from a T to C substitution at nucleotide position 47, causing the leucine (L) at amino acid position 16 to be replaced by a proline (P). 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	Uncertain	0.43
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.071	.;T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.066	D
MetaRNN	Pathogenic	0.88	D;D
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	0.99	D;D
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.5	N;N
REVEL	Uncertain	0.47
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.014	D;D
Polyphen		0.98	D;D
Vest4		0.65
MutPred		0.74		Loss of stability (P = 0.0064);Loss of stability (P = 0.0064);
MVP		0.82
MPC		0.24
ClinPred		0.90	D
GERP RS		3.8
Varity_R		0.68
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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.

Other links and lift over

hg19: chr17-28659105;