3-11839304-T-C

Position:

• chr3-11839304-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_001284401.2(TAMM41):​c.329A>G​(p.Tyr110Cys) variant causes a missense change involving the alteration of a conserved nucleotide. 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 Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAMM41 NM_001284401.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 7.54

Genes affected

TAMM41 (HGNC:25187): (TAM41 mitochondrial translocator assembly and maintenance homolog) Predicted to enable phosphatidate cytidylyltransferase activity. Predicted to be involved in CDP-diacylglycerol biosynthetic process and cardiolipin biosynthetic process. Predicted to be located in mitochondrial inner membrane. Predicted to be extrinsic component of mitochondrial inner membrane. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.98
• PP5: Variant 3-11839304-T-C is Pathogenic according to our data. Variant chr3-11839304-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 1299473.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAMM41	NM_001284401.2	c.329A>G	p.Tyr110Cys	missense_variant	3/8	ENST00000455809.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAMM41	ENST00000455809.6	c.329A>G	p.Tyr110Cys	missense_variant	3/8	3	NM_001284401.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Combined oxidative phosphorylation deficiency 56 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 27, 2022

- -

Dysphagia;C1145670:Respiratory failure;C1865916:Bilateral ptosis;C4317146:Gastroesophageal reflux Pathogenic:1

Pathogenic, no assertion criteria provided

research

Institut IMAGINE, Institut National de la Sante et de la Recherche Medicale

Aug 01, 2021

Functional validation in a Saccharomyces cerevisiae strain deleted of TAM4: the mutant cDNA failed to reverse the growth defect of the yeast with the tam41 gene deleted -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	28
DANN	Uncertain	1.0
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Pathogenic	0.30	D
MetaRNN	Pathogenic	0.98	D;D;D
MetaSVM	Uncertain	0.23	D
MutationAssessor	Pathogenic	3.8	H;H;H
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-8.5	D;D;D
REVEL	Pathogenic	0.83
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	.;.;D
Vest4		0.96
MutPred		0.91		Gain of methylation at K109 (P = 0.0394);Gain of methylation at K109 (P = 0.0394);Gain of methylation at K109 (P = 0.0394);
MVP		0.88
MPC		0.84
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.96
gMVP		0.94

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-11880778;