chr3-44357757-A-G

Variant names:

• chr3-44357757-A-G
• rs919903477
• NM_173826.4:c.46A>G

Variant summary

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

The NM_173826.4(TCAIM):​c.46A>G​(p.Ile16Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,614,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TCAIM NM_173826.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.12
• Publications: 0 publications found

Genes affected

TCAIM (HGNC:25241): (T cell activation inhibitor, mitochondrial) Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173826.4. 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
	TCAIM	NM_173826.4	MANE Select	c.46A>G	p.Ile16Val	missense	Exon 3 of 11	NP_776187.2	Q8N3R3-1
	TCAIM	NM_001282913.2		c.46A>G	p.Ile16Val	missense	Exon 3 of 11	NP_001269842.1	Q8N3R3-1
	TCAIM	NM_001029839.3		c.46A>G	p.Ile16Val	missense	Exon 3 of 4	NP_001025010.1	Q8N3R3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCAIM	ENST00000342649.9	TSL:1 MANE Select	c.46A>G	p.Ile16Val	missense	Exon 3 of 11	ENSP00000341539.4	Q8N3R3-1
	TCAIM	ENST00000383746.7	TSL:1	c.46A>G	p.Ile16Val	missense	Exon 3 of 4	ENSP00000373252.3	Q8N3R3-3
	TCAIM	ENST00000396078.7	TSL:1	c.46A>G	p.Ile16Val	missense	Exon 3 of 4	ENSP00000379388.3	Q8N3R3-3

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152214 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

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

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461794 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727194

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

American (AMR) AF: 0.0000447 AC: 2 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111974

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152214 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74370

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.000327 AC: 5 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68050

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000869

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	0.070
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.2
DANN	Benign	0.89
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.1
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.034
Sift	Benign	0.24	T
Sift4G	Benign	0.23	T
Polyphen		0.0020	B
Vest4		0.10
MutPred		0.32		Loss of catalytic residue at P18 (P = 0.0306)
MVP		0.23
MPC		0.18
ClinPred		0.024	T
GERP RS		0.52
Varity_R		0.020
gMVP		0.21
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.39		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.39		Position offset: -16

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs919903477; hg19: chr3-44399249;