rs144531991

Variant names:

• chr1-111486604-C-A
• rs144531991
• NM_020683.7:c.854G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-111486604-C-A
• chr1-111486604-C-G
• chr1-111486604-C-T

Variant summary

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

The NM_020683.7(TMIGD3):​c.854G>T​(p.Arg285Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. R285P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 30)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TMIGD3 NM_020683.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920
• Publications: 1 publications found

Genes affected

TMIGD3 (HGNC:51375): (transmembrane and immunoglobulin domain containing 3) This gene encodes a transmembrane and immunoglobulin domain-containing protein. Alternative splicing results in multiple transcript variants, one of which shares its 5' terminal exon with that of the overlapping adenosine A3 receptor gene (GeneID:140), thus resulting in a fusion product. [provided by RefSeq, Nov 2014]

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=0.07492423).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020683.7. 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
	TMIGD3	NM_020683.7	MANE Select	c.854G>T	p.Arg285Leu	missense	Exon 4 of 6	NP_065734.5
	TMIGD3	NM_001081976.3		c.611G>T	p.Arg204Leu	missense	Exon 4 of 6	NP_001075445.1	P0DMS9-1
	TMIGD3	NM_001302680.2		c.347G>T	p.Arg116Leu	missense	Exon 3 of 5	NP_001289609.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMIGD3	ENST00000369716.9	TSL:1 MANE Select	c.854G>T	p.Arg285Leu	missense	Exon 4 of 6	ENSP00000358730.4	P0DMS9-2
	TMIGD3	ENST00000369717.8	TSL:1	c.611G>T	p.Arg204Leu	missense	Exon 4 of 6	ENSP00000358731.4	P0DMS9-1
	TMIGD3	ENST00000442484.2	TSL:1	n.433G>T		non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151998 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251420 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

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: 1461518 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 727054

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.0000224 AC: 1 AN: 44720

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5590

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111888

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151998 Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1 AN XY: 74214

African (AFR) AF: 0.00 AC: 0 AN: 41366

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67990

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	0.49
DANN	Benign	0.74
DEOGEN2	Benign	0.027	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.97	T
PhyloP100		-0.092
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.074
Sift	Uncertain	0.022	D
Sift4G	Benign	0.11	T
Vest4		0.16
MutPred		0.61		Loss of MoRF binding (P = 0.027)
MVP		0.085
MPC		0.040
ClinPred		0.10	T
GERP RS		-1.9
Varity_R		0.045
gMVP		0.12
Mutation Taster		=98/2	polymorphism

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: rs144531991; hg19: chr1-112029226;