3-44400437-G-T

Variant names:

• chr3-44400437-G-T
• rs779097157
• NM_173826.4:c.968G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_173826.4(TCAIM):​c.968G>T​(p.Gly323Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. G323D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TCAIM NM_173826.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.99
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.916

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.968G>T	p.Gly323Val	missense	Exon 9 of 11	NP_776187.2	Q8N3R3-1
	TCAIM	NM_001282913.2		c.968G>T	p.Gly323Val	missense	Exon 9 of 11	NP_001269842.1	Q8N3R3-1
	TCAIM	NM_001282914.2		c.536G>T	p.Gly179Val	missense	Exon 9 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.968G>T	p.Gly323Val	missense	Exon 9 of 11	ENSP00000341539.4	Q8N3R3-1
	TCAIM	ENST00000412611.6	TSL:1	n.*544G>T		non_coding_transcript_exon	Exon 9 of 11	ENSP00000392032.2	Q8N3R3-2
	TCAIM	ENST00000412611.6	TSL:1	n.*544G>T		3_prime_UTR	Exon 9 of 11	ENSP00000392032.2	Q8N3R3-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461510 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727076

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39602

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111852

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.058	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.0
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.99	D
Vest4		0.71
MutPred		0.79		Gain of sheet (P = 0.0344)
MVP		0.72
MPC		0.79
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.83
gMVP		0.78
Mutation Taster		=30/70	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: rs779097157; hg19: chr3-44441929;