rs1288620763

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-42313417-C-A
• chr19-42313417-C-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>A​(p.Pro14Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P14L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM145 NM_173633.3 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.17615986).

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>A	p.Pro14Gln	missense	Exon 1 of 15	NP_775904.2	Q8NBT3
	TMEM145	NM_001366910.1		c.41C>A	p.Pro14Gln	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>A	p.Pro14Gln	missense	Exon 1 of 15	ENSP00000301204.2	Q8NBT3
	TMEM145	ENST00000673205.1		c.41C>A	p.Pro14Gln	missense	Exon 1 of 14	ENSP00000499841.1	A0A5F9ZGX1
	TMEM145	ENST00000673187.1		c.41C>A	p.Pro14Gln	missense	Exon 1 of 15	ENSP00000500040.1	A0A5F9ZH48

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152126 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000165 AC: 2 AN: 1214682 Hom.: 0 Cov.: 30 AF XY: 0.00000168 AC XY: 1 AN XY: 594180

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: 18250

East Asian (EAS) AF: 0.0000365 AC: 1 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: 0.00 AC: 0 AN: 3384

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

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

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152126 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74298

African (AFR) AF: 0.0000241 AC: 1 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.16
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.097
Sift	Benign	0.22	T
Sift4G	Benign	0.19	T
Polyphen		0.93	P
Vest4		0.45
MutPred		0.22		Loss of catalytic residue at P14 (P = 0.005)
MVP		0.54
MPC		0.48
ClinPred		0.35	T
GERP RS		0.87
PromoterAI		-0.18	Neutral
Varity_R		0.087
gMVP		0.30
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;