17-30325071-C-A

Variant names:

• chr17-30325071-C-A
• rs767179206
• NM_206832.3:c.385G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_206832.3(TMIGD1):​c.385G>T​(p.Asp129Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. D129N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TMIGD1 NM_206832.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.383
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.111326545).

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>T	p.Asp129Tyr	missense	Exon 4 of 7	NP_996663.1	Q6UXZ0-1
	TMIGD1	NM_001319942.2		c.385G>T	p.Asp129Tyr	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.385G>T	p.Asp129Tyr	missense	Exon 4 of 7	ENSP00000332404.4	Q6UXZ0-1
	TMIGD1	ENST00000854986.1		c.385G>T	p.Asp129Tyr	missense	Exon 4 of 7	ENSP00000525045.1
	TMIGD1	ENST00000538566.6	TSL:2	c.385G>T	p.Asp129Tyr	missense	Exon 4 of 6	ENSP00000446118.2	Q6UXZ0-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250930 AF XY: 0.00000737

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: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461044 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726758

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33414

American (AMR) AF: 0.00 AC: 0 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111532

Other (OTH) AF: 0.00 AC: 0 AN: 60356

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0556734), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.73	T
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.38
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.093
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.0010	B
Vest4		0.41
MutPred		0.40		Loss of disorder (P = 0.038)
MVP		0.42
MPC		0.20
ClinPred		0.58	D
GERP RS		-0.98
Varity_R		0.090
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs767179206; hg19: chr17-28652089; COSMIC: COSV105195700;