3-44396784-G-C

Variant names:

• chr3-44396784-G-C
• NM_173826.4:c.835G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173826.4(TCAIM):​c.835G>C​(p.Val279Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TCAIM NM_173826.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07505426).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCAIM	NM_173826.4	c.835G>C	p.Val279Leu	missense_variant	Exon 8 of 11	ENST00000342649.9	NP_776187.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCAIM	ENST00000342649.9	c.835G>C	p.Val279Leu	missense_variant	Exon 8 of 11	1	NM_173826.4	ENSP00000341539.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461868 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.8
DANN	Benign	0.87
DEOGEN2	Benign	0.011	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.75	.;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.075	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.57	N;N
REVEL	Benign	0.10
Sift	Benign	0.31	T;T
Sift4G	Benign	0.29	T;T
Polyphen		0.0	B;B
Vest4		0.11
MutPred		0.26		Loss of catalytic residue at V279 (P = 0.0083);Loss of catalytic residue at V279 (P = 0.0083);
MVP		0.14
MPC		0.21
ClinPred		0.051	T
GERP RS		-3.1
Varity_R		0.034
gMVP		0.24

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-44438276;