3-11844891-T-C

Variant names:

• chr3-11844891-T-C
• rs392621
• ENST00000417723.1:n.*17A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000417723.1(TAMM41):​n.*17A>G variant causes a splice region, non coding transcript exon 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. 3/3 splice prediction tools predict no significant impact on normal splicing. 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 ENST00000417723.1 splice_region, non_coding_transcript_exon
• Scores: Splicing: ADA: 0.00004400
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322
• Publications: 14 publications found

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]

TAMM41 Gene-Disease associations (from GenCC):

• combined oxidative phosphorylation deficiency 56

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TAMM41	NM_001284401.2	c.136-680A>G		intron_variant	Intron 1 of 7	ENST00000455809.6	NP_001271330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAMM41	ENST00000455809.6	c.136-680A>G		intron_variant	Intron 1 of 7	3	NM_001284401.2	ENSP00000398596.1

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

GnomAD2 exomes AF: 0.412 AC: 55083 AN: 133782 AF XY: 0.424

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 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

African (AFR) AF: 0.273 AC: 2348 AN: 8612

American (AMR) AF: 0.314 AC: 8543 AN: 27232

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 5047 AN: 10770

East Asian (EAS) AF: 0.265 AC: 2436 AN: 9200

South Asian (SAS) AF: 0.476 AC: 28402 AN: 59714

European-Finnish (FIN) AF: 0.456 AC: 5808 AN: 12746

Middle Eastern (MID) AF: 0.566 AC: 1573 AN: 2778

European-Non Finnish (NFE) AF: 0.456 AC: 72460 AN: 158824

Other (OTH) AF: 0.438 AC: 6235 AN: 14224

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

African (AFR) AF: 0.262 AC: 10843 AN: 41444

American (AMR) AF: 0.378 AC: 5776 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1688 AN: 3472

East Asian (EAS) AF: 0.253 AC: 1308 AN: 5170

South Asian (SAS) AF: 0.465 AC: 2239 AN: 4818

European-Finnish (FIN) AF: 0.450 AC: 4741 AN: 10546

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31174 AN: 67938

Other (OTH) AF: 0.436 AC: 921 AN: 2112

Alfa AF: 0.416 Hom.: 5712

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
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs392621; hg19: chr3-11886365;