NM_173633.3:c.41C>T

Variant names:

• chr19-42313417-C-T
• rs1288620763
• NM_173633.3:c.41C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173633.3(TMEM145):​c.41C>T​(p.Pro14Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000165 in 1,214,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: TMEM145 NM_173633.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.157
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08123124).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173633.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM145	NM_173633.3	MANE Select	c.41C>T	p.Pro14Leu	missense	Exon 1 of 15	NP_775904.2	Q8NBT3
	TMEM145	NM_001366910.1		c.41C>T	p.Pro14Leu	missense	Exon 1 of 15	NP_001353839.1	A0A5F9ZH48

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM145	ENST00000301204.8	TSL:2 MANE Select	c.41C>T	p.Pro14Leu	missense	Exon 1 of 15	ENSP00000301204.2	Q8NBT3
	TMEM145	ENST00000673205.1		c.41C>T	p.Pro14Leu	missense	Exon 1 of 14	ENSP00000499841.1	A0A5F9ZGX1
	TMEM145	ENST00000673187.1		c.41C>T	p.Pro14Leu	missense	Exon 1 of 15	ENSP00000500040.1	A0A5F9ZH48

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000165 AC: 2 AN: 1214684 Hom.: 0 Cov.: 30 AF XY: 0.00000168 AC XY: 1 AN XY: 594182

African (AFR) AF: 0.00 AC: 0 AN: 24278

American (AMR) AF: 0.00 AC: 0 AN: 13586

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18252

East Asian (EAS) AF: 0.00 AC: 0 AN: 27426

South Asian (SAS) AF: 0.00 AC: 0 AN: 51132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37686

Middle Eastern (MID) AF: 0.000296 AC: 1 AN: 3384

European-Non Finnish (NFE) AF: 0.00000101 AC: 1 AN: 989868

Other (OTH) AF: 0.00 AC: 0 AN: 49072

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0070	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.16
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	0.82	N
REVEL	Benign	0.073
Sift	Benign	0.81	T
Sift4G	Benign	1.0	T
Polyphen		0.0020	B
Vest4		0.24
MutPred		0.23		Loss of loop (P = 0.0073)
MVP		0.41
MPC		0.51
ClinPred		0.15	T
GERP RS		0.87
PromoterAI		-0.055	Neutral
Varity_R		0.063
gMVP		0.26
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1288620763; hg19: chr19-42817569;