3-11844891-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001284401.2(TAMM41):c.136-680A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 456,078 control chromosomes in the GnomAD database, including 42,293 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.39 (12245 hom., cov: 32)
  • Exomes 𝑓: 0.44 (30048 hom.)
• Consequence: TAMM41 NM_001284401.2 intron
• Scores: Splicing: ADA: 0.00004400
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAMM41	NM_001284401.2	c.136-680A>G		intron_variant		ENST00000455809.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAMM41	ENST00000455809.6	c.136-680A>G		intron_variant		3	NM_001284401.2	P1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59264 AN: 151860 Hom.: 12246 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.432

GnomAD3 exomes AF: 0.412 AC: 55083 AN: 133782 Hom.: 11937 AF XY: 0.424 AC XY: 30908 AN XY: 72866

Gnomad AFR exome AF: 0.269

Gnomad AMR exome AF: 0.314

Gnomad ASJ exome AF: 0.470

Gnomad EAS exome AF: 0.262

Gnomad SAS exome AF: 0.477

Gnomad FIN exome AF: 0.451

Gnomad NFE exome AF: 0.461

Gnomad OTH exome AF: 0.442

GnomAD4 exome AF: 0.437 AC: 132852 AN: 304100 Hom.: 30048 Cov.: 0 AF XY: 0.445 AC XY: 77028 AN XY: 173194

Gnomad4 AFR exome AF: 0.273

Gnomad4 AMR exome AF: 0.314

Gnomad4 ASJ exome AF: 0.469

Gnomad4 EAS exome AF: 0.265

Gnomad4 SAS exome AF: 0.476

Gnomad4 FIN exome AF: 0.456

Gnomad4 NFE exome AF: 0.456

Gnomad4 OTH exome AF: 0.438

GnomAD4 genome AF: 0.390 AC: 59274 AN: 151978 Hom.: 12245 Cov.: 32 AF XY: 0.389 AC XY: 28917 AN XY: 74272

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.436

Alfa AF: 0.421 Hom.: 3453

Bravo AF: 0.375

Asia WGS AF: 0.397 AC: 1381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	11
Dann	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000044
dbscSNV1_RF	Benign	0.0060
SpliceAI score (max)		0.15		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: rs392621; hg19: chr3-11886365;