3-44396425-C-T

Variant names:

• chr3-44396425-C-T
• rs888077386
• NM_173826.4:c.721C>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_173826.4(TCAIM):​c.721C>T​(p.His241Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TCAIM NM_173826.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.82
• 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_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.943

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.721C>T	p.His241Tyr	missense	Exon 7 of 11	NP_776187.2	Q8N3R3-1
	TCAIM	NM_001282913.2		c.721C>T	p.His241Tyr	missense	Exon 7 of 11	NP_001269842.1	Q8N3R3-1
	TCAIM	NM_001282914.2		c.289C>T	p.His97Tyr	missense	Exon 7 of 11	NP_001269843.1	Q8N3R3-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCAIM	ENST00000342649.9	TSL:1 MANE Select	c.721C>T	p.His241Tyr	missense	Exon 7 of 11	ENSP00000341539.4	Q8N3R3-1
	TCAIM	ENST00000412611.6	TSL:1	n.*297C>T		non_coding_transcript_exon	Exon 7 of 11	ENSP00000392032.2	Q8N3R3-2
	TCAIM	ENST00000412611.6	TSL:1	n.*297C>T		3_prime_UTR	Exon 7 of 11	ENSP00000392032.2	Q8N3R3-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Uncertain	0.38
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.056	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.8
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.88
MutPred		0.83		Loss of disorder (P = 0.0313)
MVP		0.81
MPC		0.87
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.64
gMVP		0.84
Mutation Taster		=12/88	disease causing

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: rs888077386; hg19: chr3-44437917;