chr3-44357757-A-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173826.4(TCAIM):​c.46A>C​(p.Ile16Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. I16V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: TCAIM NM_173826.4 missense
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05033803).

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>C	p.Ile16Leu	missense	Exon 3 of 11	NP_776187.2	Q8N3R3-1
	TCAIM	NM_001282913.2		c.46A>C	p.Ile16Leu	missense	Exon 3 of 11	NP_001269842.1	Q8N3R3-1
	TCAIM	NM_001029839.3		c.46A>C	p.Ile16Leu	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>C	p.Ile16Leu	missense	Exon 3 of 11	ENSP00000341539.4	Q8N3R3-1
	TCAIM	ENST00000383746.7	TSL:1	c.46A>C	p.Ile16Leu	missense	Exon 3 of 4	ENSP00000373252.3	Q8N3R3-3
	TCAIM	ENST00000396078.7	TSL:1	c.46A>C	p.Ile16Leu	missense	Exon 3 of 4	ENSP00000379388.3	Q8N3R3-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000479 AC: 7 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: 0.00 AC: 0 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: 0.00000630 AC: 7 AN: 1111974

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	10
DANN	Benign	0.84
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.1
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.026
Sift	Benign	0.15	T
Sift4G	Benign	0.54	T
Polyphen		0.0080	B
Vest4		0.22
MutPred		0.30		Loss of catalytic residue at P18 (P = 0.0306)
MVP		0.30
MPC		0.21
ClinPred		0.026	T
GERP RS		0.52
Varity_R		0.040
gMVP		0.27
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs919903477; hg19: chr3-44399249;