Variant 3-44862100-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144638.3(TMEM42):c.176T>C(p.Leu59Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000436 in 916,388 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000044 ( 0 hom. )

Consequence

TMEM42
NM_144638.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.918

Variant links:

Genes affected

TMEM42 (HGNC:28444): (transmembrane protein 42) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM42 links:

KIF15 (HGNC:17273): (kinesin family member 15) Predicted to enable microtubule binding activity and microtubule motor activity. Predicted to be involved in microtubule-based movement. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

KIF15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM42	NM_144638.3 linkuse as main transcript	c.176T>C	p.Leu59Pro	missense_variant	1/3	ENST00000302392.5	NP_653239.1
KIF15	XR_007095708.1 linkuse as main transcript	n.4368-6391T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TMEM42	ENST00000302392.5 linkuse as main transcript	c.176T>C	p.Leu59Pro	missense_variant	1/3	1	NM_144638.3	ENSP00000306564	P1
TMEM42	ENST00000477126.1 linkuse as main transcript	n.197T>C		non_coding_transcript_exon_variant	1/2	1
KIF15	ENST00000422209.1 linkuse as main transcript	c.*59+9306T>C		intron_variant, NMD_transcript_variant		3		ENSP00000391205

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000667

AC:

AN:

44978

Hom.:

AF XY:

0.0000393

AC XY:

AN XY:

25476

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000837

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000436

AC:

AN:

916388

Hom.:

Cov.:

AF XY:

0.00000464

AC XY:

AN XY:

431220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000446

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000296

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 11, 2023

The c.176T>C (p.L59P) alteration is located in exon 1 (coding exon 1) of the TMEM42 gene. This alteration results from a T to C substitution at nucleotide position 176, causing the leucine (L) at amino acid position 59 to be replaced by a proline (P). 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

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.59

M_CAP

Pathogenic

0.57

MetaRNN

Uncertain

0.56

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-4.1

REVEL

Uncertain

0.32

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.60

MutPred

0.74

Gain of relative solvent accessibility (P = 0.005);

MVP

0.067

MPC

0.97

ClinPred

0.66

GERP RS

2.9

Varity_R

0.95

gMVP

0.80

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over