chr17-30329376-C-G

Variant names:

• chr17-30329376-C-G
• NM_206832.3:c.236G>C

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.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. 14/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.457
• 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: 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=0.15199715).

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.236G>C	p.Gly79Ala	missense	Exon 3 of 7	NP_996663.1	Q6UXZ0-1
	TMIGD1	NM_001319942.2		c.236G>C	p.Gly79Ala	missense	Exon 3 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.236G>C	p.Gly79Ala	missense	Exon 3 of 7	ENSP00000332404.4	Q6UXZ0-1
	TMIGD1	ENST00000854986.1		c.236G>C	p.Gly79Ala	missense	Exon 3 of 7	ENSP00000525045.1
	TMIGD1	ENST00000538566.6	TSL:2	c.236G>C	p.Gly79Ala	missense	Exon 3 of 6	ENSP00000446118.2	Q6UXZ0-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727244

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: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

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: 1112008

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

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-0.46
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.095
Sift	Benign	0.074	T
Sift4G	Benign	0.17	T
Polyphen		0.97	D
Vest4		0.18
MutPred		0.23		Loss of ubiquitination at K77 (P = 0.0738)
MVP		0.10
MPC		0.035
ClinPred		0.74	D
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

Other links and lift over

hg19: chr17-28656394;