3-44865160-C-T

Position:

• chr3-44865160-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144638.3(TMEM42):​c.460C>T​(p.Leu154Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TMEM42 NM_144638.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.265

Genes affected

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

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04489255).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM42	NM_144638.3	c.460C>T	p.Leu154Phe	missense_variant	3/3	ENST00000302392.5	NP_653239.1
KIF15	XR_007095708.1	n.4368-3331C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM42	ENST00000302392.5	c.460C>T	p.Leu154Phe	missense_variant	3/3	1	NM_144638.3	ENSP00000306564	P1
TMEM42	ENST00000477126.1	n.2561C>T		non_coding_transcript_exon_variant	2/2	1
KIF15	ENST00000422209.1	c.*60-8169C>T		intron_variant, NMD_transcript_variant		3		ENSP00000391205

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

Jan 10, 2023

The c.460C>T (p.L154F) alteration is located in exon 3 (coding exon 3) of the TMEM42 gene. This alteration results from a C to T substitution at nucleotide position 460, causing the leucine (L) at amino acid position 154 to be replaced by a phenylalanine (F). 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	Benign	0.072
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.032	N
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.044
Sift	Benign	0.24	T
Sift4G	Benign	0.20	T
Polyphen		0.19	B
Vest4		0.037
MutPred		0.16		Gain of ubiquitination at K152 (P = 0.0594);
MVP		0.014
MPC		0.34
ClinPred		0.19	T
GERP RS		1.3
Varity_R		0.058
gMVP		0.20

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: chr3-44906652;