17-30324891-C-G

Variant names:

• chr17-30324891-C-G
• rs1309060550
• NM_206832.3:c.565G>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_206832.3(TMIGD1):​c.565G>C​(p.Asp189His) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. D189N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TMIGD1 NM_206832.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.10
• Publications: 0 publications found

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

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.982

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.565G>C	p.Asp189His	missense	Exon 4 of 7	NP_996663.1	Q6UXZ0-1
	TMIGD1	NM_001319942.2		c.565G>C	p.Asp189His	missense	Exon 4 of 6	NP_001306871.1	Q6UXZ0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMIGD1	ENST00000328886.5	TSL:1 MANE Select	c.565G>C	p.Asp189His	missense	Exon 4 of 7	ENSP00000332404.4	Q6UXZ0-1
	TMIGD1	ENST00000854986.1		c.565G>C	p.Asp189His	missense	Exon 4 of 7	ENSP00000525045.1
	TMIGD1	ENST00000538566.6	TSL:2	c.565G>C	p.Asp189His	missense	Exon 4 of 6	ENSP00000446118.2	Q6UXZ0-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251396 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461864 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727234

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	0.43	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.1
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Pathogenic	0.81
Sift	Benign	0.33	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.96
MutPred		0.91		Loss of ubiquitination at K184 (P = 0.0665)
MVP		0.74
MPC		0.23
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.57
gMVP		0.77

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

Other links and lift over

dbSNP: rs1309060550; hg19: chr17-28651909;