19-42314328-C-G

Position:

• chr19-42314328-C-G

Variant summary

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

The NM_173633.3(TMEM145):​c.177C>G​(p.Phe59Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM145 NM_173633.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.944

Genes affected

TMEM145 (HGNC:26912): (transmembrane protein 145) Predicted to be involved in G protein-coupled receptor signaling pathway and response to pheromone. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM145 (HGNC:):

ACMG classification

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
TMEM145	NM_173633.3	c.177C>G	p.Phe59Leu	missense_variant	2/15	ENST00000301204.8	NP_775904.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM145	ENST00000301204.8	c.177C>G	p.Phe59Leu	missense_variant	2/15	2	NM_173633.3	ENSP00000301204.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

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

Apr 06, 2023

The c.177C>G (p.F59L) alteration is located in exon 2 (coding exon 2) of the TMEM145 gene. This alteration results from a C to G substitution at nucleotide position 177, causing the phenylalanine (F) at amino acid position 59 to be replaced by a leucine (L). 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	0.99
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;.
Eigen	Benign	0.047
Eigen_PC	Benign	0.0073
FATHMM_MKL	Benign	0.41	N
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;.
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.6	D;.
REVEL	Benign	0.17
Sift	Uncertain	0.015	D;.
Sift4G	Uncertain	0.019	D;D
Polyphen		0.97	D;.
Vest4		0.58
MutPred		0.29		Loss of methylation at R56 (P = 0.1469);Loss of methylation at R56 (P = 0.1469);
MVP		0.27
MPC		1.3
ClinPred		0.99	D
GERP RS		1.1
Varity_R		0.52
gMVP		0.60

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: chr19-42818480;