3-11790537-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001284401.2(TAMM41):c.982A>C(p.Met328Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TAMM41 NM_001284401.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.88

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3000328).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAMM41	NM_001284401.2	c.982A>C	p.Met328Leu	missense_variant	8/8	ENST00000455809.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAMM41	ENST00000455809.6	c.982A>C	p.Met328Leu	missense_variant	8/8	3	NM_001284401.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Sep 01, 2021

The c.919A>C (p.M307L) alteration is located in exon 7 (coding exon 7) of the TAMM41 gene. This alteration results from a A to C substitution at nucleotide position 919, causing the methionine (M) at amino acid position 307 to be replaced by a leucine (L). 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
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
Cadd	Uncertain	24
Dann	Benign	0.97
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.97	D;D
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.064
Sift	Benign	0.038	D;D
Sift4G	Benign	0.090	T;T
Vest4		0.50
MVP		0.53
MPC		0.35
ClinPred		0.99	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.26

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: chr3-11832011;