3-44400507-T-A

Position:

• chr3-44400507-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000342649.9(TCAIM):​c.1038T>A​(p.Asp346Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TCAIM ENST00000342649.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.08

Genes affected

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

TCAIM (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038900852).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCAIM	NM_173826.4	c.1038T>A	p.Asp346Glu	missense_variant	9/11	ENST00000342649.9	NP_776187.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCAIM	ENST00000342649.9	c.1038T>A	p.Asp346Glu	missense_variant	9/11	1	NM_173826.4	ENSP00000341539.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 26, 2024

The c.1038T>A (p.D346E) alteration is located in exon 9 (coding exon 8) of the TCAIM gene. This alteration results from a T to A substitution at nucleotide position 1038, causing the aspartic acid (D) at amino acid position 346 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.6
DANN	Benign	0.78
DEOGEN2	Benign	0.023	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.67	.;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.039	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.52	N;N
REVEL	Benign	0.038
Sift	Benign	0.64	T;T
Sift4G	Benign	0.75	T;T
Polyphen		0.0010	B;B
Vest4		0.14
MutPred		0.32		Gain of methylation at R351 (P = 0.1603);Gain of methylation at R351 (P = 0.1603);
MVP		0.11
MPC		0.20
ClinPred		0.054	T
GERP RS		-4.1
Varity_R		0.025
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1702005655; hg19: chr3-44441999;