rs392621

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-11844891-T-A
• chr3-11844891-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000417723.1(TAMM41):​n.*17A>T 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 0.00000329 in 304,192 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000033 (0 hom.)
• Consequence: TAMM41 ENST00000417723.1 splice_region, non_coding_transcript_exon
• Scores: Splicing: ADA: 0.00009145
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000329 AC: 1 AN: 304192 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 173236

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 8620

American (AMR) AF: 0.00 AC: 0 AN: 27246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10772

East Asian (EAS) AF: 0.00 AC: 0 AN: 9210

South Asian (SAS) AF: 0.00 AC: 0 AN: 59722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12750

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2778

European-Non Finnish (NFE) AF: 0.00000629 AC: 1 AN: 158866

Other (OTH) AF: 0.00 AC: 0 AN: 14228

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.5
DANN	Benign	0.50
PhyloP100		-0.32

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000091
dbscSNV1_RF	Benign	0.0060
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: rs392621; hg19: chr3-11886365;